Controlled release core-shell particles and suspensions including the same

ABSTRACT

Provided is a composition including a dispersion medium including: an aqueous solution; a first active ingredient; a flavor agent; and a first type of polymer; and a dispersed phase including: a population of particles, each particle including: a core including: a second active ingredient a second type of polymer; and an aqueous solution; a shell, substantially surrounding the core, the shell including: a third type of polymer; a plurality of lipophilic carriers; and a third active ingredient; and a plurality of emulsifying agents.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation of U.S. Non-Provisionalapplication Ser. No. 17/020,693, filed 14 Sep. 2020, titled CONTROLLEDRELEASE CORE-SHELL PARTICLES AND SUSPENSIONS INCLUDING THE SAME. U.S.Non-Provisional application Ser. No. 17/020,693 claims the benefit ofU.S. Provisional Patent Applications 62/899,595, filed 12 Sep. 2019,titled ALIMENTARY-RELATED PARTICLES, PRODUCTION METHODS, AND PRODUCTIONAPPARATUS; 62/944,912, filed 6 Dec. 2019, titled ALIMENTARY-RELATEDPARTICLES, PRODUCTION METHODS, AND PRODUCTION APPARATUS; 62/968,591,filed 31 Jan. 2020, titled ALIMENTARY-RELATED PARTICLES, PRODUCTIONMETHODS, AND PRODUCTION APPARATUS, and 63/012,058, filed 17 Apr. 2020,titled ALIMENTARY-PRODUCT RELATED PARTICLES, PRODUCTION METHODS, ANDPRODUCTION APPARATUS. The entire content of each afore-listedearlier-filed application is hereby incorporated by reference for allpurposes.

BACKGROUND 1. Field

The present disclosure relates generally to alimentary products and,more specifically, to alimentary products encapsulating nutrients orother payloads.

2. Description of the Related Art

Encapsulation of one substance in another may take a variety of forms.Often, encapsulation involves entrapping or otherwise enveloping aliquid, solid, or gas (referred to as the core material, internal phase,first phase, or payload, interchangeably) in an enclosing materialcommonly referred to as the carrier, particle, shell, wall, capsule ormembrane interchangeably. Historically, certain types of encapsulation,and particularly those with limited or no mouthfeel imparted bycapsules, were regarded as commercially infeasible in the food andbeverage industry for many use cases due to cost, shelf stability, andvarious other challenges.

SUMMARY

The following is a non-exhaustive listing of some aspects of the presenttechniques. These and other aspects are described in the followingdisclosure.

Some aspects include a composition including a dispersion mediumincluding: an aqueous solution; a first active ingredient; a flavoragent; and a first type of polymer; and a dispersed phase including: apopulation of particles, each particle including: a core including: asecond active ingredient a second type of polymer; and an aqueoussolution; a shell, substantially surrounding the core, the shellincluding: a third type of polymer; a plurality of lipophilic carriers;and a third active ingredient; and a plurality of emulsifying agents.

BRIEF DESCRIPTION OF THE DRAWINGS

The above-mentioned aspects and other aspects of the present techniqueswill be better understood when the present application is read in viewof the following figures in which like numbers indicate similar oridentical elements:

FIG. 1 is a schematic diagram that illustrates a miscible single-phaseparticle, in accordance with some embodiments of the present disclosure;

FIG. 2 is a schematic diagram that illustrates a miscible single-phaseparticle with core-shell structure, in accordance with some embodimentsof the present disclosure;

FIG. 3 is a cross section view of an immiscible single-phase particle,in accordance with some embodiments of the present disclosure;

FIG. 4 is a cross section view of an immiscible double-phase particlewith core-shell structure, in accordance with some embodiments of thepresent disclosure;

FIG. 5 is a cross section view of a W/O/W droplet, in accordance withsome embodiments of the present disclosure;

FIG. 6 is a cross section view of a particle with a core and two layers,in accordance with some embodiments of the present disclosure;

FIG. 7 is a schematic diagram that illustrates a particle with adispersed phase, containing an encapsulant, a continuous phase, and alayer surrounding the continuous phase, in accordance with someembodiments of the present disclosure;

FIG. 8 is a schematic diagram that illustrates a multi-layer particlewith a core and three layers surrounding the core, in accordance withsome embodiments of the present disclosure;

FIG. 9 is a schematic diagram that illustrates a solid particle having adispersed phase, containing an encapsulant, and a continuous phase, inaccordance with some embodiments of the present disclosure;

FIG. 10 is a schematic diagram that illustrates a solid particle with adispersed phase, containing an encapsulant, a continuous phase, and twolayers surrounding the continuous phase, in accordance with someembodiments of the present disclosure;

FIG. 11 is a flow diagram showing a method for preparing a particle, inaccordance with some embodiments of the present disclosure;

FIG. 12 is a flow diagram showing a method of operation, in accordancewith some embodiments of the present disclosure; and

FIG. 13 is a perspective view of a container with particles dispersed ina medium, in accordance with some embodiments of the present disclosure.

While the present techniques are susceptible to various modificationsand alternative forms, specific embodiments thereof are shown by way ofexample in the drawings and will herein be described in detail. Thedrawings may not be to scale. It should be understood, however, that thedrawings and detailed description thereto are not intended to limit thepresent techniques to the particular form disclosed, but to thecontrary, the intention is to cover all modifications, equivalents, andalternatives falling within the spirit and scope of the presenttechniques as defined by the appended claims.

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

To mitigate the problems described herein, the inventors had to bothinvent solutions and, in some cases just as importantly, recognizeproblems overlooked (or not yet foreseen) by others in the field of thefood and beverage industry or the flavoring industry. Indeed, theinventors wish to emphasize the difficulty of recognizing those problemsthat are nascent and will become much more apparent in the future shouldtrends in industry continue as the inventors expect. Further, becausemultiple problems are addressed, it should be understood that someembodiments are problem-specific, and not all embodiments address everyproblem with traditional systems described herein or provide everybenefit described herein. That said, improvements that solve variouspermutations of these problems are described below.

Headings are used below to orient the reader. The introduction insection 1 generally describes issues addressed by embodiments in each ofthe sections that follow. Section 2, labeled particles, discussesparticles surrounded by a liquid medium, and section 3 discussessolid-state particles, like powders. Section 4 discusses materials withwhich the particles in sections 2 and 3 may be made, and sections 5 and6 discuss size and stability properties of those particles. Section 7explains the theory underlying these embodiments, and section 8discusses mixing techniques by which the particles in sections 2 and 3may be manufactured. Sections 9, 10, 11, and 12 describe taste,permeability, release time profiles, and bio-availability of alimentaryproducts with the particles of sections 2 and 3. Section 13 describesexamples of alimentary and non-alimentary products in which thepreviously described compositions may be used, and finally, section 14describes various ways of characterizing the particles, how to use theparticles of sections 2 and 3, and how the particles of sections 2 and 3operate, in some embodiments.

1. Introduction

Some forms of encapsulation are used in pharmaceuticals for variouspurposes. For example, particles with controlled-release mechanisms areused to provide a steady delivery of drugs to the body. Other examplesinclude using smart particles, containing cancer drugs. Thesetechniques, however, are generally not suitable for use in the food andbeverage industry due to the high cost of manufacturing or expensivematerials required for encapsulation.

To the extent encapsulation technology is used in food and beverageindustry, the particles are either too large (e.g., may be felt in themouth of the user, often with particles so large as to lead to beunpleasant) or are only capable of encapsulating a limited number ofingredients. An example is microencapsulation of fish oils to fortifybread. Encapsulation mitigates or eliminates the fishy aroma and tasteof such oils, with an added benefit of less susceptibility to oxidationand less development of rancidity. However, techniques to manufacturesuch particles are capable of encapsulating only water-insolublecargoes. Another example is cannabidiol (CBD)-infused beverages whereinan emulsion of CBD particles are stabilized in water via various typesof surfactants. Emulsification techniques, used to manufactureCBD-infused beverages, may produce stable emulsions with particles onlyin the size range of tens of nanometers. Bigger particles often may notbe stabilized with this technique because the stabilizer agent used inthese techniques are small molecule surfactants that cannot stabilizeparticles in the size range of hundreds of microns. This is believed tolimit the amount of cargo that may be encapsulated and added into abeverage. In addition, many of these techniques are also limited toencapsulation of water-insoluble cargoes. (None of which is to suggestthat any subject matter is disclosed here or anywhere else in thisdocument where tradeoffs are discussed.)

Thus, existing approaches to encapsulate ingredients with food-gradeencapsulants are either too expensive, have short shelf-life, or produceparticles that are too large to remain un-noticed by the consumer. Aneed exists for a technique to manufacturing small particles, capable ofencapsulating a variety of water-insoluble and water-miscibleingredients, which may be dispersed in a variety of mediums, iscost-compatible with margins in the food and beverage industry, andproduces a smaller or no change in the mouth-feel and quality of thehost material.

Some embodiments mitigate the above described issues with traditionalencapsulation processes. Some embodiments incorporate a variety ofnutrients, nootropics, functional ingredients, flavoring agents,intoxicants, stimulants, or other payloads in particles that may beadded to various food and beverage products without detrimentallyaffecting the mouth-feel of the host material.

Some embodiments produce particles containing a variety of ingredients.In some embodiments, particles may mask the flavor of the encapsulatedingredients, control the release kinetics of the encapsulatedingredients after consumption, control the delivery location of theencapsulated ingredients, stabilize the encapsulated ingredients in thehost material, prolong the shelf life of the encapsulated ingredients,or enhance the bioavailibity of the encapsulated ingredients.

In some embodiments, particles may mask the flavor of the encapsulatedingredients, in some cases making the taste of those ingredients almostunnoticeable for the consumer. For example, some embodiments areexpected to mask the bitter taste of vodka (or tequila, gin, rum, grainalcohol, or the like) in a beverage (e.g., water, juice, soda, or othermixers) by encapsulating the vodka in the particles, dispersed in a hostbeverage, by maintaining a barrier between the vodka and the consumer'staste buds, until the particles rupture or dissolve in the digestivetract to release their encapsulants. In some embodiments, only some ofthe vodka may be encapsulated to mitigate the effect of the taste ofvodka. In some embodiments, the taste of vodka is expected to be reducedfor a given concentration of vodka in a beverage. For instance, whentested by a panel of adult subjects given a blind taste test, it isexpected that more than half will report a lower-concentration of vodkain a beverage subject to the present treatment relative to a controlbeverage with substantially the same concentration of vodka (e.g.,within 5%)—a test protocol that applies to other assertions of change intaste where unless another protocol is specified.

In some embodiments, particles may delay the release of encapsulatedingredients into the host medium in which the particles are dispersed.In some embodiments, delayed release is used to mask the flavor of theencapsulated components. In some embodiments, the delayed release isused to slow down the digestion and absorption of the encapsulatedingredients inside the body. In some embodiments, the particles are madeof pH triggered materials, whereby the particles release theencapsulated ingredients in media with specific pH ranges. In someembodiments, the particles are tuned to release the encapsulatedingredients in acidic environment of the stomach or the intestine. Insome embodiments, the particles are made of enzyme-digestible materials,whereby the particles release the encapsulated ingredients in presenceof enzymes. In some cases, such enzymes are available enzymes in thedigestive tract. In some embodiments, the particles are made ofmaterials that dissolve in presence of digestive juices from thepancreas, liver, and intestine, whereby releasing the encapsulatedingredients.

In some embodiments, the particles protect an encapsulated ingredientfrom structural damage before or after consumption. For example,probiotics may be damaged and deactivated in acidic environment of thedigestive tract before reaching the small intestine. By encapsulatingprobiotics, a particle can deliver probiotics without any damage to thesmall intestine by preventing a direct interaction between theprobiotics and the digestive tract until the particle reaches the smallintestine and starts releasing the encapsulated probiotics. In someembodiments, particles may be made of (full particle or only some of thelayers of the particle) a polymer which degrades in the presence ofbacterial enzymes with a pH-independent polymer. Such polymers cancontrol the release of the encapsulants in a pre-determined site of thedigestive tract (e.g. in the distal large intestine, beginning at thececum, and continuing through the ascending, transverse, and descendingcolon, and ending in the sigmoid colon.)

In some embodiments, the particles keep an immiscible componentdispersed in a host solution. For example, cannabidiol (CBD) oil isimmiscible in a variety of water-based beverages, like water, sodas,beer, wine, liquor, fruit juice, seltzer, smoothies, kombucha, and thelike. By encapsulating CBD oil, a stable emulsion of CBD oil droplets,encapsulated inside a polymeric shell, in a water-based beverage isexpected to be obtainable (e.g., with less than half of the CBD oilseparating out at a 1% concentration by mass over one week at roomtemperature). In some embodiments, the particles have a hydrophilicexterior that makes them soluble (e.g., component is regarded as solubleif more than a 0.1% concentration by mass is stable at room temperature,unless another criteria for solubility is specified by industrystandards for a particular host beverage at issue, in which case theindustry practice governs) and dispersible in water-based solutions.

In some embodiments, the particles prolong the shelf life ofencapsulants by protecting the encapsulants from direct interaction withthe surrounding medium. For example, particle may hinder exposure of theencapsulants to moisture or oxygen and prolong the shelf life.

In some embodiments, the particles increase the bioavailibity of theencapsulants. For example, bioavailability of cannabidiol (CBD) oil isincreased by encapsulating the CBD oil in water soluble small particles(e.g. 50 nm, 100 nm, or 200 nm). In some embodiments, a bioavailabilityof an ingredient may be increased by encapsulating the ingredient in aparticle that has bioavailability enhancer compounds.

The particles may be added to, formed within, or contain, various hostfood or beverage products or other alimentary products. In someembodiments, these particles may be added to, formed within, or containvarious drugs and other pharmaceutical products.

2. Particles

In some embodiments, a particle is referred to as globular if thelength-width ratio (meaning the ratio of the length (largest dimension)of the particle divided by the width (smallest dimension) which is fixedat an angle of 90° in relation to the length) is less than about 4. Thelength-width ratio of a globular particle may be less than about 3, 2,1.8, 1.5, 1.2, or 1.1. Some embodiments have globular particles.

In some embodiments, a particle may be a capsule having a boundary wall(e.g. shell) that defines (and separates) an interior and exterior ofthe respective capsule. In some embodiments, the boundary shell may havemultiple layers.

In some embodiments, a particle may be made of droplets. In someembodiments, a particle may be formed of a droplet with a stabilizinglayer covering the droplet. In some embodiments, the stabilizing layeris a polymeric shell. In some embodiments, the stabilizing layer may beformed of stabilizing agents, such as a surfactant, coated on thedroplet. In some embodiments, the stabilizing layer may be made of animpermeable material. For example, a droplet of aqueous solution may becovered by a layer of oil acting as the boundary wall. In someembodiments, the stabilizing layer may be formed of a plurality ofabove-mentioned embodiments.

In some embodiments, some of the layers may be separating layers (e.g.seal coat) between the layer (or core) containing the encapsulant andanother layer (e.g. the delayed release layer). The functions of aseparating layer may be to provide a smooth base for the application ofthe delayed release layer, to prolong the core's (or internal layers)resistance to various conditions (e.g. acidic, neutral, enzymes), and toimprove stability by inhibiting any interaction between the encapsulantsand the delayed release layer. In some embodiments, a seal layer may beused to separate any two layer of a multi-layer particle or to provide aseal between the particle and the surrounding medium. In someembodiments, a seal layer (e.g. a water-permeable diffusion barrier) maycontain a water insoluble material such as a wax, a fatty alcohol,shellac, zein, polyvinylpyrrolidonc, a water insoluble cellulosederivative, ethyl cellulose, a polymethacrylate, or methyl cellulose.

In some embodiments, a particle may contain some active ingredients,referred to as the encapsulants, and some non-active ingredients,referred to as fillers.

In some embodiments, particles may have a boundary wall that defines(and separates) an interior and exterior of the respective particle. Theinterior may contain an “encapsulant,” which is the material inside theparticle's boundary, as distinct from the boundary wall itself.

In some embodiments, a boundary wall that defines (and separates) aninterior and exterior of the respective particle is made of encapsulant.In some embodiments, a boundary wall that defines (and separates) aninterior and exterior of the respective particle is partially made ofencapsulant. For example, droplets of CBD oil may be formed in anaqueous solution through emulsification process and the droplet may bestabilized by stabilizing agents. In this example, the boundary may beinclude (e.g., consist of) a stabilizing agent and CBD oil.

In some embodiments, a boundary wall that defines (and separates) aninterior and exterior of the respective particle may be made of, atleast in part, a polymeric shell. In some embodiments, there may be aconcentration gradient of the encapsulants in the boundary wall. In someembodiments, the concentration of the encapsulants decreases across theboundary wall with higher concentration in regions of the boundary wallcloser to the interior and lower concentrations in the regions of theboundary wall closer to the exterior of the particle.

In some embodiments, a particle may not have a defined boundary wall andthe encapsulants might be evenly distributed throughout the particle. Aparticle may be made of filler that serve to retain the shape of theparticle while maintaining the encapsulants inside the particle. In someembodiments, there are no chemical or electrical (e.g., ion sharing)reactions between the fillers and the encapsulants. In some embodiments,the particles are held together and the encapsulants are retained withinthe particles by the structural framework provided by the fillers.

2.1. Miscible Single-Phase Particles

FIG. 1 illustrates a particle 100 containing fillers 101 andencapsulants 102. In some embodiments, fillers 101 may include a solventthat is miscible in the medium surrounding the particle 100, within theparticle 100. Fillers 101 may further include a polymer that can inhibitthe diffusion and dispersion of the encapsulants 102 in the mediumsurrounding 103 the particle, like a host beverage in which the particle100 has been dispersed.

In some embodiments, the permeability of the encapsulants 102 to thesurrounding medium depends on many factors including size of theencapsulants 102, pore size of the particle 100, the temperature,viscosity of the fillers 101 and the surrounding medium, and size of theparticle 100.

In some embodiments, a particle 100 may be formed by dispersing theencapsulants 102 in a polymer, forming droplets of this mixture and thencuring the polymer. For example, a droplet of sodium alginate solution,containing the encapsulants 102, may be added to a solution containingcalcium ions. Upon entry of the droplet, alginate chains startcrosslinking as the calcium ions diffuse toward the droplet. Aftersufficient time, the whole droplet with transform to a particle 100 andthe encapsulants may be trapped inside a gel of calcium alginate. Inanother example, an encapsulant 102 may be mixed with a temperaturecurable polymer and a particle 100 may be formed upon elevating thetemperature.

FIG. 2 illustrates a particle 200, having a shell 201 and a core 202,containing encapsulants 102. In some embodiments, both the shell 201 andthe core 202 may include a solvent that is miscible in the mediumsurrounding the particle 200. Each the shell 201 and the core 202 mayfurther included a polymer that can inhibit the diffusion and dispersionof the encapsulants 102 in the medium 203 surrounding the particle. Insome embodiments, the shell 201 is configured to have a lowerdiffusivity coefficient to inhibit the diffusion and dispersion of theencapsulants 102 in the surrounding medium. In particles structurallysimilar to particle 200, both the shell 201 and the core 202 may beconsidered fillers.

In some embodiments, particle 200 may be formed by dispersing theencapsulants 102 in a solution, forming droplets of this mixture andthen adding these droplets into a polymer solution. For example, adroplet of a solution containing calcium ions and encapsulants 102(referred to as the first solution) may be added to a second solutioncontaining sodium alginate chains. Upon entry of the droplet to thesecond solution, the alginate chains in the vicinity of the droplet withstart to crosslink as they interact with the calcium ions diffusing fromthe droplet. Over time, a shell of cross-linked alginate chains may beformed around the droplet. The formed alginate shell may produce aparticle 200 containing the encapsulants 102 that are entrapped by theshell 201. The thickness of the shell may depend on many parametersincluding the concentration of calcium ions, the concertation of sodiumalginate in the second solution, temperature, pH, size of the droplet,presence of any other chemical that may affect discussion of calciumions and alginate chains, and presence of any other chemical that mayreact with ios or alginate chains.

In some embodiments, a droplet may be formed by various techniques.Droplet formation, in some use cases, is expected to affectencapsulation efficiency and final product stability. Some types ofdroplet formation are achieved by drop-wise addition of a first solutionto a second solution. Drop-wise addition is expected to form bigdroplets in the size range of a few centimeters (again, discussion ofwhich is not to be read as a disclaimer of any subject matter). In somecases, the drops may have the size properties of the particle discussedabove.

Some embodiments are expected to mitigate these issues with drop-wiseaddition by using a tube with an orifice, like pipettes, needles, ormicro needles (which may be generally referred to as pipettes) to formthe droplets in the size range of a millimeter or less (or the othersize ranges discussed above). In some embodiments, food-grade pressurepumps (such as syringe pumps, and peristaltic pumps) fluidically couplea reservoir of the first solution to an orifice disposed within or abovea second reservoir of the second solution. The orifice may have adiameter in the range of hundreds of micrometers, and the orifice maygenerally have a circular or oval shape. The pressure pump may becoupled to an actuator configured to pump the first solution into thesecond solution at a volumetric flow rate of 1-1000 ml per minute perorifice. In operation, the pump may push the first solution from thefirst reservoir and introduce it to the second solution in the secondreservoir in the form of droplets.

In some embodiments, a particle 200 may be formed by a reversespherification process. Reverse spherification is best understood withcontrast to direct spherification. In direct spherification, a drop ofthe encapsulants by a film of non-calcium alginate is dropped into abath containing a source of calcium ions. On the other hand, in reversespherification, the encapsulants may be first mixed with a source ofcalcium or magnesium ions, for example, calcium chloride. This phase isreferred to as first phase or interior phase. If the encapsulants is aliquid food product, the calcium or magnesium salt may be used to avoidaffecting the flavor of the liquid food product. Next, a drop or otherquantity of a monolithic body of the first phase may be formed with themixture including the encapsulants and the calcium or magnesium ions.The drop may then be introduced (e.g., as a drop falling through airdown into a volume of liquid, or formed immersed within such a receivingvolume of liquid) into a solution containing a non-calcium alginate, forexample, sodium alginate. This solution is referred to as the secondphase or exterior phase. When a surface of the formed drop containingcalcium ions comes into contact with the solution containing alginate, asemi-solid and gelatinous film may be formed almost instantaneously,which contains in its interior the encapsulants.

In some embodiments, sodium alginate (e.g., in the range of 0.01 to 1 wt%) may added to the first phase immediately before addition to thesecond phase. Presence of alginate chains inside the particle may helpwith structural stability and delayed release kinetics. In some otherembodiments, other types of polymers, instead of alginate chains areadded to the first phase.

2.2. Immiscible Single-Phase Particles

In some embodiments, manufacturing a particle may include obtaining anoil-in-water (O/W) emulsion. O/W emulsions may include liquid oildroplets dispersed in a continuous liquid water phase. O/W emulsions maybe formed from two immiscible or nearly immiscible water and oil phases.The oil phase may include a lipophilic solvent or a suspension carrier.The oil phase may further include water-immiscible or nearlywater-immiscible encapsulants. The oil phase may further includesurfactants and emulsifiers that may facilitate the formation of O/Wemulsions by decreasing the interfacial tension between the water andoil phases and further decreasing the energy input required to form O/Wdroplets. The surfactants may further stabilize the O/W emulsions. Thesurfactants may include hydrophobic segments that orient in the oilphase and a hydrophilic segment that orient in the water phase. Thesurfactants or emulsifiers may enhance the stability of the O/Wemulsions. The water phase may also contain surfactants or emulsifiersthat may facilitate the formation of O/W emulsions by decreasing theinterfacial tension between the water and oil phases and furtherdecreasing the energy input required to form O/W droplets.

O/W emulsions may be made by pre-processing the oil phase and waterphase with a variety of techniques prior to combination. In someembodiments, the oil phase may be heated to 50° C., 70° C., 90° C., 110°C., 130° C., 150° C., 200° C., or 250° C. prior to emulsification. Thismay be done to dissolve various types of fillers (e.g. surfactants,polymers, and waxes) and encapsulants. In some embodiments, the waterphase may be heated to heated to 50° C., 60° C., 70° C., 80° C., 90° C.,or 95° C. prior to emulsification. In some embodiments, the heatingprocess may be done to dissolve various types of fillers (e.g.,surfactants). In some embodiments, the heating process may be performedat ambient pressure. In some embodiments, the heating process may beperformed at pressurized containers (e.g. 1.5 atm, 2 atm, 5 atm, or 10atm). In some embodiments, the heating process may be done to controlthe viscosity of the oil phase. Temperature ranges may be selected basedon the type and amount of chemicals being added to the oil phase or tothe water phase. For instance, for some of the types and amounts ofsurfactant described below, temperatures outside these ranges areexpected to cause either incomplete solubility (or miscibility) belowthe low end of the temperature range, or degradation of the chemicalstructure of the surfactant molecule above the high end, none of whichis to suggest that any subject matter is disclaimed, either here orelsewhere in this document.

In some embodiments, emulsification may be carried out at roomtemperature (herein defined as 25° C.).

In some embodiments, emulsification may be carried out at temperaturesabove room temperature, e.g., between 26 to 100° C. In some embodiments,the emulsification temperature (of the combined input phases) may bebetween 30 to 80° C. In some embodiments, the emulsification temperaturemay be between 40 to 60° C. Emulsification in temperatures above roomtemperature may be done to reduce the viscosity of oil and water phases.This may be done to reduce the interfacial viscosity between the oil andwater phases. In some embodiments, emulsification in temperatures aboveroom temperature may be done to provide better mixing of the oil andwater phases by tuning the viscosity or density of the phases.

In some embodiments, emulsification may be carried out in temperaturesat or below room temperature. In some embodiments, the emulsificationtemperature may be between 1 to 24° C. In some embodiments, theemulsification temperature may be between 5 to 20° C. In someembodiments, the emulsification temperature may be between 10 to 15° C.This may be done to reduce the collision rate of formed droplets, whichmay produce a more stable emulsion than higher-temperature processes.Emulsification in temperatures below room temperature may be done toavoid overheating and subsequent destabilization of the emulsion.

In some embodiments, the oil phase (e.g., prior to introduction to thewater phase) comprises a lipophilic solvent or suspension carrier. Inembodiments where the immiscibility of the water and oil phases is ofimportance, lipophilic solvents may be selected. In embodiments wherethe oil-soluble encapsulants' stability in the oil phase may beaffected, a compatible suspension carrier may be selected.

In some embodiments, the volume ratio of the oil phase to water phasemay be between 1:1 to 1:20. In some embodiments, the volume ratio of theoil phase to water phase may be between 1:2 to 1:15. In someembodiments, the volume ratio of the oil phase to water phase may bebetween 1:3 and 1:4. In some embodiments, the volume fraction of thedispersed phase (e.g., oil) is reduced to achieve smaller droplet size.This reduction may be done so as to decrease emulsion viscosity. Thisreduction may be done so as to increase emulsifier availability perdroplet. This reduction may also be done so as to protect the O/Wemulsions against coalescence due to reduced rate of collisionfrequency.

In some embodiments, where Cannabis extract or isolate is among theencapsulants, the amount of carrier oil in the formulation may exceedthat of the Cannabis extract or isolate. In some embodiments, the oilphase may include 50-60 w/w % long chain triglycerides (LCT) to preventor impede Ostwald ripening as well as to help achieve smaller dropletsize.

In some embodiments, cannabidiol (CBD) may be dispersed in the carrieroil of the oil phase, as an encapsulant. The concentration of CBD in theoil phase may range between 1 to 40 w/w % (percentage weight of CBD toweight of oil phase). In some embodiments, the concentration of CBD inoil phase may range between 5 to 50 w/w %. In some embodiments, theconcentration of CBD in oil phase may range between 10 to 25 w/w %.Higher CBD concentrations may result in higher CBD loading per oildroplet.

An example procedure for producing CBD-containing emulsions may includethe following steps: first, an oil phase and an aqueous phase may beprepared separately under continuous magnetic stirring at about 80 and50° C. respectively. The oil phase may consist of medium-chaintriglyceride (MCT) oil or other biocompatible oils and various types ofsurfactants. The aqueous phase may contain additives, such ashydrophilic surfactants (e.g., tween 20) or glycerol. All components maybe completely dissolved. Subsequently, the two phases may be combinedand mixed with a mechanical mixer. This pre-homogenization can beperformed by employing a high-shear rotor-stator device such as anUltra-Turrax available from IKA®-Werke GmbH & CO. KG of Staufen,Germany. Thus, a homogenous, but coarse emulsion with droplet sizes of afew microns may be produced. This pre-emulsion may be further stirredand re-heated to around 50° C. Although higher temperatures of over 90°C. have been used for this production step, moderate heating may be usedto avoid degradation of phospholipids. The emulsion may then beprocessed with a high-pressure homogenization device, such as ahigh-energy ultrasonicator.

In some embodiments, the emulsions may be stabilized by surfactants.Surfactants may include a lipophilic segment and a hydrophilic segment,which may facilitate the formation of oil droplets dispersed in thecontinuous water phase. In some embodiments, the emulsions arestabilized by stabilizers. The stabilizers may be non-surface-activemacromolecules that are added to increase the viscosity of thecontinuous phase and that reduce the mobility of the droplets in orderto prevent the droplets from coalescing. In some embodiments, thecontinuous phase is the phase in which the particles are dispersed inafter purification and rinsing. In some other embodiments, thecontinuous phase is the exterior phase in the emulsification.

In some embodiments, a single surfactant system is used to formoil-in-water particles. In some embodiments, the surfactants aredispersed in the oil phase. Soybean lecithin is an example of aningredient suitable for such a system. In some embodiments, thesurfactants are dispersed in the water phase. In some embodiments, thesurfactants are dispersed in both oil and water phases.

In some embodiments, the viscosity of the dispersed phase (internalphase) is expected to influence droplet disruption. In some embodiments,the viscosity of the continuous phase (external phase) is expected tonot influence droplet disruption, provided energy density is constantand coalescence is avoided.

In some embodiments, a weighting agent is added to the oil phase. Insome embodiments, the addition of the weighting agent is to match thedensity of the oil phase with the density of the water phase. Examplesof such weighting agents are sucrose acetate isobutyrate ester gum,brominated vegetable oil, or any other oil soluble ingredient withdensities higher than water.

In some embodiments, the oil phase is an oil that is water-immiscible orhas very low water solubility (e.g., less than 1 gram in 100 grams ofwater, or less than 5 grams in 100 grams of water, or less than 10 gramsin 100 grams of water). Examples of such oils include cannabidiol (CBD)oil, hemp oil, soybean oil, safflower oil, sunflower oil, castor oil,corn oil, olive oil, palm oil, peanut oil, almond oil, sesame oil,rapeseed oil, peppermint oil, poppy seed oil, canola oil, hydrogenatedvegetable oils, fish oil, borage oil, palm kernel oil, hydrogenatedsoybean oil, coconut oil, cottonseed oil, glyceryl esters of saturatedfatty acids, glyceryl behenate, glyceryl distearate, glycerylmonolinoleate, glyceryl palminate, glyceryl palmitostearate, glycerylricinoleate, glyceryl stearate, polyglyceryl 10-oleate, polyglyceryl3-oleate, polyglyceryl 4-oleate, glyceryl isostearate, glyceryl laurate,glyceryl monooleate, polyglyceryl 10-tetralinoleate, behenic acid,caprylyic/capric glycerides, and any combinations thereof.

In some embodiments, the oil and water phases are heated to 70-250° C.and 40-90° C. prior to emulsification, respectively. In someembodiments, the oil and water phases are cooled to lower temperatures(e.g. room temperature or 50° C.) prior to emulsification.

In some embodiments, a rotor stator mixer is used to prepare theemulsions. The rotation of the impeller may impart high-shear force tothe immiscible phases and causes the formation of oil droplets in acontinuous water phase.

The carrier oil may be selected from a group of food-grade medium-chaintriglycerides (MCTs, e.g., coconut oil) or long-chain triglycerides(LCTs, e.g. olive oil). The oil phase may contain the encapsulants(e.g., CBD), and the encapsulants content may range between 5-50 wt % ofthe particle. In some embodiments, the amount of carrier oil in theformulation may somewhat exceed that of the encapsulants.

In some embodiments, the volume fraction of the dispersed phase (e.g.,oil) is minimized to achieve smaller droplet size. This may be due todecrease in emulsion viscosity, increased emulsifier availability perdroplet (e.g. particle), and protection against coalescence due toreduced rate of collision frequency.

In some embodiments, the phases are added to a working volume of ahigh-shear rotor-stator device that is used to create O/W emulsions. Avariety of stirrers, blenders and homogenizers may be used for thepurpose of creating emulsions. The final size and distribution ofparticles may be directly influenced by the size and polydispersityindex (PDI) of emulsion droplets.

In some embodiments, the mechanical mixer is a rotor-stator device witha speed that is set to between 6,000 to 12,000 RPM. In some embodiments,the dispersed (e.g., oil) phase may be added in a drop-wise fashion tothe continuous phase (e.g., aqueous phase).

In some embodiments, the emulsification is performed in an ice bath sothat the agitation is carried at a temperature below room temperature.In some embodiments, the emulsification is performed in an oil bath witha temperature above room temperature.

FIG. 3 illustrates an example cross-section of a particle 300 formed byoil-in-water emulsification. The O/W droplets consists of an oil phase301 which contains encapsulants 102. The hydrophobic part of thesurfactants 303 may be positioned in the oil phase 301, while thehydrophilic segment of the surfactant 304 may be positioned in the waterphase 304.

In some embodiments, a particle formed from a droplet with somestabilizing agent (e.g., surfactant) placed in the interphase of thedroplet and the surrounding medium.

In some embodiments, the oil phase may be the continuous phase and thewater phase may be the dispersed phase.

2.3. Immiscible Double-Phase Particles

FIG. 4 illustrates an example cross-section of a particle 400 with twolayers. Such particles 400 may include a core 401, which may containencapsulants (e.g., a payload) 402, and a shell 403. In someembodiments, the shell 403 does not contain any encapsulants. In someembodiments, the shell 403 also contain encapsulants.

In some embodiments, a particle 400 may be formed by a double emulsionprocess. FIG. 5 illustrates an example cross-section of W/O/W droplets500. The W/O/W droplets may include an inner water phase 501 thatcontains encapsulants (e.g., payload or active ingredients) 502. Thehydrophobic part of a first type of surfactant 503, stabilizing the W/Oemulsion, may be positioned in the oil phase 3104, while the hydrophilicsegment of the surfactant 3103 may be positioned in the inner waterphase 501. The hydrophobic part of a second type of surfactant 505stabilizing the W/O/W droplets may be positioned in the oil phase 504,while the hydrophilic part of the surfactant 505 may be positioned inthe outer water phase 506.

In some embodiments, particles 400 may be packaged or added toadditional alimentary products before packaging. In some cases,flavoring agents are added. In some cases, the packages are liquidcontainers of less than 50, 10, 5, 1, or 0.5 liters in size made ofplastic, aluminum, glass, or cardboard. In some cases, the container mayhave an interior lining. In some cases, the resulting beverage is shelfstable for more than 2 days, 7 days, 14 days, 1 month, 2 months, 6months, or 12 months in these containers at room temperature or coldchain (e.g. below 15° C., 10° C., or 5° C.). In some cases, the filledcontainers may be distributed to retail stores, placed on shelves, andsold, or distributed directly to other businesses or consumers.

In some embodiments, the particles similar to the particle shown in FIG.4 are packaged in 2 oz. (or 1 oz.) format to deliver 20 mg ionic zinc,1000 mg vitamin C, 600 IU and vitamin D3. In some embodiments, the 2 oz.format contain 20 mg CBD as well.

In some embodiments, particles are added to a beverage and packaged in 1ml, 1.2 ml, 1 oz., 8 oz., 16 oz. or 24 oz.

In some embodiments related to water/oil/water (W/O/W) emulsions, alipophilic emulsifier 503 may be used to prepare the primary W/Oemulsion and a hydrophilic emulsifier 505 to prepare the secondaryemulsion. The fundamental molecular and colloidal factors influencingthe coalescence stability of the inner and outer droplets, whenconsidered separately and in isolation, are similar to those for simpleW/O (water in oil, having oil as the continuous phase) and O/W (oil inwater, having water as the continuous phase) emulsions, respectively.However, there is the additional aspect involved with in the W/O/Wemulsion that the emulsifiers of different hydrophile-lipophile balancetend to have a destabilizing effect on each another. Ideally, thelipophilic emulsifier would remain located entirely at the inneroil-water interface. But, in practice, in order to be able to make theprimary emulsion droplets sufficiently small, it is often helpful forthe lipophilic emulsifier to be present at rather high concentrations inthe oil phase. In the self-assembled form of aggregates and reversemicelles, this excess lipophilic emulsifier may enhance thesolubilization and mass transport of water-soluble compounds (includingions) through the oil phase. In addition, some of the excess lipophilicemulsifier inevitably migrates to the outer oil-water interface, therebyundermining the stabilizing ability of the hydrophilic secondaryemulsifier.

Relevant to some embodiments, a stability parameter characterizing theeffectiveness of any double emulsion formulation is the ‘yield.’ This isthe percentage of primary emulsion aqueous phase that is retained asinternal aqueous phase in the W/O/W emulsion following the second-stageemulsification. The yield may be determined by measuring the extent ofaccumulation in the outer continuous phase of a marker compoundoriginally present in the aqueous phase of the primary W/O emulsion.

An initial yield of 100% would mean that all the dispersed aqueous phaseof the original primary emulsion remained undisturbed during the secondemulsification stage. In practice, the initial yield value typicallylies below this ideal theoretical limit. This is because of thedisruption of some inner droplets induced by the hydrodynamic conditionspresent during the secondary emulsification stage, in many embodiments.During storage of a double emulsion, there may be then a gradual fall inthe value of the percentage yield as the internal aqueous phase isreleased into the external continuous phase.

Some embodiments include W/O/W emulsions containing an inner waterphase. The inner water phase may be aqueous or gelled. The inner waterphase may contain encapsulants. The inner water phase may containsurfactants. The inner water phase may contain various type ofmacromolecules and polymers. The oil phase may contain surfactants,encapsulants, and various type of macromolecules and polymers. The outerwater phase may contain surfactants, stabilizers and various type ofmacromolecules and polymers. W/O/W particles may mask the flavor of theencapsulated components and make the taste of those components almostunnoticeable for a consumer in an alimentary product containing theW/O/W emulsions.

In some embodiments, the particles may be used to mask the flavor of theencapsulated components during consumption by a consumer. For example,the bitter taste of vodka can be masked in a beverage by encapsulatingthe vodka in the particles and dispersing them in a beverage. As aconsumer is drinking the beverage, the taste of vodka is significantlymasked, and the consumer mainly tastes the flavor of the beverage. Incontrast, in the absence of such particles, the taste of vodka would bemuch stronger at the same concentration. In some embodiments, theparticles have a polymer shell that can delay the release ofencapsulated components to the solution in which the capsules aredispersed. This provides a timeframe for a consumer to drink such asolution without tasting the flavor of the encapsulated components.

In some embodiments, the inner water phase may contain proteins asencapsulants. The concentration of proteins may range between 1-80 wt %.

In some embodiments, the solvent for the aqueous phase in the primaryW/O emulsion may include water, a mixture of ethanol and water, or pureethanol.

In some embodiments, to stabilize the primary W/O emulsion, polyglycerolpolyricinoleate (PGPR) may be used. This particular lipophilicemulsifier may be used in the formulation of W/O/W emulsions forfood-based applications. This synthetic emulsifier is polyglycerol esterof polyricinoleic acid. PGPR is expected to be effective for stabilizingfine W/O emulsions made with triglyceride oils.

In some embodiments, to stabilize the primary W/O emulsion, PGPRconcentration of 0.1-10 wt % may be used in the lipophilic part of theemulsion. In some embodiments, PGPR concentration may range between 2-8wt %. In some embodiments, PGPR concentration may range between 4-6 wt%.

In some embodiments, to stabilize the W/O emulsions,phosphatidylcholine-depleted lecithin may be used as an alternative toaddition to to PGPR (which is not to suggest that other describedfeatures are not also amenable to variation).

In some embodiments, polymers may be used to stabilize the doubleemulsions. Three expected benefits of using polymers as stabilizingingredients in double emulsions are:

-   -   a. Compared with small-molecule emulsifiers, polymers are much        less susceptible to diffusion and migration from internal to        external aqueous phases, or vice versa;    -   b. Polymers may readily form stabilizing network structures in        the dispersed and continuous aqueous phases, e.g., viscoelastic        solutions and gels; and    -   c. Surface-active biopolymers may be used as effective        stabilizers of the outer oil-water interface of W/O/W emulsion        droplets.

In addition to the technical benefits (mention of which is not intendedto suggest that embodiments not affording these benefits or otherbenefits discussed herein are disclaimed), the incorporation of polymers(e.g., biopolymers) as functional ingredients in double emulsions mayallow for the reduced use of synthetic emulsifiers in such formulationsand possibly even for their complete elimination from food-and-beveragebased applications.

Various food biopolymers may be used in W/O/W. Examples include gelatin,casein, whey protein, bean protein, Acacia gum, and xanthan. Thesebiopolymers may increase the yield of encapsulation and also improveboth quiescent and shear-induced coalescence stability, though again,embodiments exhibiting lower yield and not using this technique are alsocontemplated, which is not to suggest that any other aspect of thisdisclosure is limiting.

In some embodiments, polylactide, polyglycolide, and their copolymerspoly(lactide-coglycolide), polycaprolactones, polyacrylates, ornonbiodegradable such as: polyacrylics, poly(vinyl chloride-co-acetate)and polystyrene are used. For instance, polyesters may be used for drugdelivery due to their biocompatibility and biodegradability.

In some embodiments, a combination of PGPR and biopolymers may be usedto stabilize the primary W/O emulsions.

In embodiments where a combination of PGPR and biopolymers may be usedto stabilize the primary W/O emulsion, the same encapsulation yield maybe achieved even at a lower concentration of PGPR. For instance, in W/Oemulsions prepared with PGPR as lipophilic emulsifier, the incorporationof 0.5 wt % of sodium caseinate in the internal aqueous phase isexpected to allow a reduction in the PGPR content from 6 to 3 wt %without affecting the yield or stability.

In some embodiments where biopolymers are used as additionalstabilizers, the initial yield may increase with increasing biopolymerconcentration. The combination of caseinate+PGPR may produce a moreviscoelastic adsorbed layer which resists the release of theencapsulants from the inner droplets. Another functional role of sodiumcaseinate in W/O/W emulsions may be as a chelating agent which mayreduce the rate of release of encapsulated multivalent cations (e.g.ionic zinc, ionic magnesium, ionic iron, etc.).

In some embodiments, a polymer shell may be coated on the particle tocontrol the release kinetics of the encapsulated ingredients. Therelease kinetics may be controlled by tuning the thickness of thepolymeric shell, the dissolution rate of the polymer in the digestivetract, or the pore sizes of the polymeric shell. Examples of suchpolymers are sodium alginate and polyethylene glycol.

In some embodiments, the inner aqueous phase may be converted into softsolid-like phase to provide long-term stability to the inner emulsionW/O droplets. This may be achieved using a biopolymer that is readilyconverted to the gel state (e.g. by thermal processing). Adopting thisapproach, a W/O/W emulsion containing a heat-set gel of whey protein inthe inner droplets can be successfully prepared by incorporating wheyprotein isolate (e.g. WPI; 15 wt %) in the primary W/O emulsion and thensubjecting the W/O emulsion to thermal treatment (80° C. for 20 min)prior to secondary emulsification. Another example of polymer may beagar to be incorporated in the inner aqueous phase.

In some embodiments, the gelation of a solution of gelatin (5 wt %)encapsulated in the internal aqueous phase is exploited in order tocontrol stability and encapsulation efficiency. Double emulsions withgelled starch within the inner droplets generally show improvedstability. The emulsification of the aqueous phase in the oil may beperformed at a temperature (e.g., 85° C.) above the melting temperatureof the starch gel, and subsequent gelation may be induced by cooling. Insome embodiments, cooling may be performed quickly (e.g., more than 10°C. drop in temperature per minute). In some other embodiments, thecooling rate may be slower (e.g., less than 5° C. drop in temperatureper minute). A benefit of starch incorporation is expected in termsencapsulation efficiency: The measured release rate of a hydrophiliccompound (e.g., alcohol or protein) from the internally gelled W/O/Wemulsions expected to be slower than for the equivalent non-gelledemulsions. However, it should be noted that the presence of the starchmay lead to some complications in the formulation of the doubleemulsion. The high viscosity of the aqueous phase increases the amountof surfactant needed for the emulsification and stabilization of the W/Odroplets. An additional factor contributing to greater surfactant demandis some complexation between the starch and the non-ionic surfactants(span 80 and tween 20).

In some embodiments, another biopolymer-based material that may beincorporated in the internal aqueous phase of a W/O/W emulsion ismicrocrystalline cellulose.

In some embodiments, emulsification of the primary W/O emulsion may becarried out in room temperature. In some cases where heat-sensitivecomponents (e.g., ethanol) are present in some embodiments, theemulsification temperature may be kept close to room temperature (e.g.,±5° C. of room temperature as defined above) to avoid or reducepotential loss of the aqueous phase.

In some embodiments, where alcohol is present in the aqueous phase, LCTs(e.g., olive oil) may be used as the oil phase solvent, for instance, toavoid or reduce the solubility of the aqueous and oil phases.

In some embodiments, the carrier oil may be food-grade. In someembodiments, the carrier oil may be selected to not adversely affectproduct quality (such as appearance, taste, texture, or stability). Insome embodiments, the carrier oil may protect from chemical degradationduring storage. In some embodiments, the carrier oil increasesbioavailability after ingestion. Carrier oils are expected to bebeneficial in stabilizing the emulsion from Ostwald ripening, which is amajor de-stabilization mechanism in nano- and micro-emulsions (again,which is not to suggest that embodiments without such carrier oils arenot also contemplated). Ostwald ripening is a process in which veryfiner droplets of emulsion dissolved into continuous phase, diffuse andredeposit upon larger droplets, thus increasing the average size ofemulsion droplets. Ostwald ripening occurs because of the increasedsolubility of the dispersed phase (e.g., oil) into the aqueous phase.This challenge can be addressed (e.g., mitigated or eliminated) by theintroduction of hydrophobic properties into the dispersed phase.

In some embodiments, hydrophobicity of the oils may be improved byintroducing a mixture of oils to produce micro- and nano-emulsions. Suchmixtures are expected to be suitable to tune the hydrophobicity to thepoint where a desired size or stability is reached for the disperseddroplets.

In some embodiments, the oil-to-water ratio by volume is between 1:1 to1:9. In addition to volume ratio, dispersed-to-continuous (e.g.,oil-to-water) phase viscosity ratio may be considered for preparingstable emulsions.

In some embodiments, a high-shear rotor-stator device may be used tocreate coarse W/O emulsions. A variety of stirrers, blenders andhomogenizers may be used for the purpose of creating emulsions (e.g.nano emulsions or micro emulsions). The size of coarse emulsion dropletsis generally in the range of 1-25 μm, depending on the type of deviceand external energy input. The final size and distribution of particlesmay be directly influenced by the size and polydispersity index (PDI) ofcoarse emulsion droplets.

In some embodiments, proteins may be used as emulsifiers for thesecondary emulsions. Proteins are expected to be highly effective assecondary emulsifying agents and as stabilizers of the outer droplets ofW/O/W emulsions. The underlying principles of the steric andelectrostatic stabilization of double emulsion droplets by protein arethe same as those relating to a simple protein-stabilized emulsion. Afurther advantage of protein as emulsifying agent is expected to be thatit is insoluble in the oil phase, and so it has little or no tendency(unlike small-molecule emulsifiers) to migrate to the internal oil-waterinterface or to interfere with the stabilization of the inner droplets.In the case of O/W emulsions, some embodiments may add polysaccharidesat low concentrations as thickening and gelling agents in order toachieve rheological control of the aqueous continuous phase; the sameapproach may be applicable to double emulsions.

Various different types of food protein emulsifiers may be employed inthe stabilization of double emulsions, including sodium caseinate,gelatin, BSA and whey protein isolate and also some hydrocolloidemulsifiers such as gum Arabic and hydrophobically modified starch. Tostabilize the outer droplets of double emulsions, various solublepolysaccharides may be utilized acting as thickening/gelling agents;pectin, carrageenan, alginate, xanthan, gellan, locust bean gum andcarboxymethylcellulose—and also using colloidal particles ofmicrocrystalline cellulose. The presence of a hydrocolloid such asmaltodextrin or gum Arabic in the external aqueous phase may be helpfulfor a W/O/W emulsion that is to be converted into microcapsules by spraydrying. With sodium caseinate as the secondary emulsifying agent,high-pressure homogenization may produce fine W/O/W emulsions and arelatively high yield.

The protein component of gum Arabic (Acacia Senegal) is expected toconfers upon this food hydrocolloid a distinctive surface activity andemulsifying properties. This same functionality can be exploited in thestabilization of the outer droplets of W/O/W emulsions. But, in contrastto a protein emulsifier such as sodium caseinate, concentrations ofaround 10 wt % of the gum are helpful in order to achieve thepreparation of fine double emulsions with good long-term stability.

In some embodiments, the combined advantages of proteins andhydrocolloids as functional ingredients may be used through thepreparation of protein—polysaccharide complexes for use as emulsifyingand stabilizing agents. In these mixed biopolymer complexes, theconstituent protein and polysaccharide molecules may be joined togetherpermanently (via covalent bonding) or reversibly (involvingelectrostatic interactions). The formation of protein—polysaccharidehybrids by controlled dry heating may be particularly convenient andbeneficial for making covalent conjugates for use in food-relatedapplications. This Maillard-type conjugation induced by the dry-heattreatment is expected to lead to improvement in protein solubility andemulsion stability under unfavorable solution conditions of low pH andhigh ionic strength. This improved functionality is believed to be dueto the increased hydrophilicity of the conjugate and its better stericstabilizing ability as compared with the protein alone.

In some embodiments, combinations of proteins and polysaccharides thatform soluble electrostatic complexes are expected to provide improvedstability properties of O/W emulsions over a wide range of environmentalconditions. Depending on the biopolymers involved and the methods usedto prepare the emulsions, the oil droplets may be coated by compositelayers or multilayers having enhanced electrosteric stabilizingproperties as compared with pure protein-stabilized emulsions. It isexpected that the same approach is also applicable to the stabilizationof W/O/W emulsions.

Various mixtures of protein+polysaccharide may be used with a purpose ofgenerating outer droplets of W/O/W emulsions that are stabilized byprotein—polysaccharide complexes. In particular, for instance, thestabilization of the external oil-water interface of double emulsions bycomplexes of WPI+xanthan gum and WPI+galactomannans (locust bean gum,guar gum and fenugreek gum) may be achieved.

In some embodiments, the nature of the composition of the emulsion maybe altered in order to minimize or reduce an amount of the composition'scalories. The reduction in size or number of oil droplets may result inloss of physical consistency and sensory properties. To mitigate thiseffect, in some embodiments, the same oil droplet size and number may beretained, but their inner part may be substituted with water. In someembodiments, the encapsulation efficiency may be sacrificed to reducethe calorie content of a particle.

In some embodiments, low-intensity homogenization is used to prepare thesecondary emulsion in order to avoid emulsion breakdown. In the initialstage of double emulsion preparation, a homogenizer of the rotor-statortype may be used to prepare the W/O (or O/W) primary emulsion. Theemulsion premix may then be subjected to high-pressure homogenization inorder to accomplish a further substantial reduction in the mean dropletsize of the inner W1 (or O1) phase. Rotor-stator equipment may be usedalso for the secondary emulsification step, but in this case under moremoderate dispersing conditions so as to try to avoid hydrodynamicconditions of intense shearing or turbulence, which may causedestabilization of the previously formed primary emulsion. Otheremulsification devices that may be used during the second stage includesonicators (operating at moderate ultrasound intensity) andhigh-pressure homogenizers (operating in a reduced pressure range).

For reliable processing during secondary emulsification, it may behelpful in some embodiments to inhibit any flow-induced coalescence ofinternal droplets with the external phase by avoiding the application ofintense hydrodynamic forces. In some implementations, this may involvesetting the applied pressures in 1-stage and 2-stage valve homogenizerswell below the values typically employed in the preparation of amicron-sized food O/W emulsion like homogenized milk.

In some embodiments, shell thickness of a particle may be 50%, 20%, 10%,or 5% of the radius of the particle.

In some embodiments, particles may have an inner volume and a boundarywall surrounding the inner volume. In some embodiments, the particlesmay have a spherical shape. In some embodiments, the particles may havea non-spherical shape. For example, the particles may have a teardrop ordouble teardrop shape.

In some embodiments, the particles may have a double shell. In someembodiments, the interior shell is an oil phase surrounding a droplet(e.g., aqueous droplet or gelled phase) in which the components to beencapsulated are dispersed. In some embodiments, the exterior shell is apolymeric shell. Such polymeric shell may be used to control the releasekinetics of the encapsulants, stabilize the particle in the surroundingmedium, or reduce the permeation of the encapsulants.

In some embodiments, the particles may have multiple shells. In someembodiments, shells may each contain similar or different types ofencapsulants. Incorporation of encapsulants at different shell may beperformed to control the release kinetics, prevent interaction of thedifferent types of encapsulants, or load different types of encapsulant,with different solubility properties (e.g., oil soluble and watersoluble), in a single particle.

In some embodiments, the encapsulants are immiscible in water. In suchinstances, in some embodiments, the encapsulants are first mixed with anorganic solvent or an oil phase; this phase may act as the interiorphase or one of the shells of a particle.

In some embodiments, a combination of polymers may be used as fillers inthe interior phase or one of the shells of a particle. For example, asecondary polymer such as chitosan may be used in addition to alginate,resulting in a polyelectrolyte complex between alginate and chitosanthat may improve the stability of the particles and reduces the porosityof them.

In some embodiments, a polymeric shell is formed around the droplet ofthe oil phase after the second emulsification. In some embodiments, thepolymeric shell may be alginate chains. Cross linking and polymerizationof a polymer are terms used interchangeably throughout this disclosure.In some embodiments, the alginate is expected to form a shell and crosslink around the droplet of the oil phase because of the diffusion of thedivalent salts such as calcium from the droplet of the oil phase. Insome embodiments, the divalent salt is dissolved in the oil phase beforethe first emulsification. In some embodiments, the divalent salt isdissolved in the oil phase after the first emulsification. In someembodiments, both the first and the second water phases comprise polymerchains and, therefore, the particle may have an interior in gelled phaseand a shell with an oil layer and then a polymer on the exterior. Insome embodiments, the polymer chains may be polymerized after the secondemulsification process. In some embodiments, the polymer chains arealginate chains. In some embodiments, the alginate may be polymerized bythe diffusion of the calcium ions, dissolved in the oil phase, to thefirst and second water phases.

In some embodiments, a polymer may be dissolved in the oil phase beforeor after the first emulsification. In some embodiments, the polymerdissolved in the oil phase may be polymerized before or after the firstemulsification to form a polymeric shell surrounding a droplet of thefirst water phase. In some embodiments, the emulsification processes maybe performed at temperatures higher than the melting temperature ofdissolved polymer in the oil phase. Once the particles are formed, thetemperature may be reduced to solidify the dissolved polymer andconsequently solidify the oil phase. Similar strategy may be used toincorporate a polymer in the inner aqueous phase (e.g., agar) andsolidify the inner aqueous phase by reducing the temperature after theemulsification steps.

In some embodiments, the oil phase may be partially removed after thesecond emulsification. In some other embodiments, the oil phase may bealmost completely removed after the second emulsification. Removal ofthe oil phase may be done to reduce the calorie content of the particle.

In some embodiments, the oil phase may be kept in the shell of theparticle to reduce the mass transfer of the encapsulated components tothe outside of the capsules. In some embodiments, the oil phase isedible. Examples of such oils are linseed oil, chia oil, coconut oil,butter, soybean, corn, orange, sunflower, olive, and perilla oil.

In some embodiments, the emulsions are stabilized by surfactants. Insome other embodiments, the emulsions are stabilized by stabilizers. Thestabilizers may be non-surface active macromolecules, which may be addedto increase the viscosity of the continuous phase and reduce themobility of droplets in order to prevent them from coalescing.

In some embodiments, electrolytes may be added to the external aqueousphase to increase adsorption density of the stabilizing agent at theoil/water interface and reduce interfacial tension in emulsions.

In some embodiments, the droplets are formed by ultrasound viaoscillations of the liquid-liquid interface during emulsificationprocess. In some embodiments, the formation of droplets is believed tobe as a consequence of unstable oscillations of the liquid-liquidinterface. These capillary waves may occur and contribute to dispersionif the diameter of droplets to be disrupted is sufficiently larger thanthe wavelength of the capillary waves (e.g., twice the length of thewavelength).

In some embodiments, the droplets are formed by ultrasound viacavitation during emulsification process. In some embodiment, someparameters positively influencing cavitation in liquids improveemulsification in terms of smaller droplet size of dispersed phase rightafter disruption. In some embodiments, imploding cavitation bubblescause intensive shock waves in the surrounding liquid and the formationof liquid jets of high liquid velocity. This may cause dropletdisruption in the vicinity of a collapsing bubble. In some embodiments,the higher the viscosity, the higher the attractive forces between themolecules and therefore, the higher the threshold intensity ofultrasound for onset of cavitation. In some embodiments, addition ofstabilizer possibly modifies and partly suppresses cavitation in thebulk of the liquid.

In some embodiments, the oil phase is an organic solvent that isimmiscible in water or has very low solubility in water (e.g., less than1 gram in 100 grams of water, or less than 5 gram in 100 grams of water,or less than 10 gram in 100 grams of water). In some other embodiments,the oil phase is includes (e.g., consists of) an organic solvent and anoil. Examples of such oils include CBD, hemp oil, fish oil, borage oil,coconut oil, cottonseed oil, soybean oil, safflower oil, sunflower oil,castor oil, corn oil, olive oil, palm oil, peanut oil, almond oil,sesame oil, rapeseed oil, peppermint oil, poppy seed oil, canola oil,palm kernel oil, hydrogenated soybean oil, hydrogenated vegetable oils,glyceryl esters of saturated fatty acids, glyceryl behenate, glyceryldistearate, glyceryl isostearate, glyceryl laurate, glyceryl monooleate,glyceryl, monolinoleate, glyceryl palmitate, glyceryl palmitostearate,glyceryl ricinoleate, glyceryl stearate, polyglyceryl 10-oleate,polyglyceryl 3-oleate, polyglyceryl 4-oleate, polyglyceryl10-tetralinoleate, behenic acid, caprylyic/capric glycerides and anycombination thereof. In some other embodiments, the oil phase may alsocontain Glycerol, Heptane, Isobutyl acetate, Anisole, Isopropyl acetate,Methyl acetate, Isoamyl alcohol, Methyl tert-butyl ether, Pentane, Ethylacetate and any combination thereof.

In some embodiments, alginate-based particles may be generated bychanneled emulsification. The two immiscible phases may be emulsifiedinto a co-flowing stream of immiscible liquid in a micro-channel inwhich the flow rates of both liquids are controlled. The alginatedroplets formed may be gelled inside or outside the channel. The meansize of the microcapsules formed may be varied over a wide range from 40to 2000 um. Owing to the micrometer-sized capillary, liquid flows inmicrofluidic devices are expected to be completely laminar, and theresulting droplets or microcapsules are expected to have very narrowsize distributions with coefficients of variance of less than 5%. Insome embodiments, the inner oil phase of the microcapsules could beremoved by extraction with propanol to prepare hollow microcapsules oraqueous-core microcapsules.

In some embodiments, capsule-shaped particles are generated bymicroemulsions preparation techniques. Calcium alginate nanoparticlesmay also be produced from microemulsions without large inputs ofmechanical energy. Unlike other emulsification techniques that involveshear force, droplet formation in microemulsions is expected tospontaneous through self-assembly. Gelation of the alginate nanodropletsmay be achieved by injecting a calcium-containing solution into the nanoemulsion. Alginate nanoparticles 100-200 nm in diameter with a PDI ofless than 0.25 are expected to be obtained.

In some embodiments, capsule-shaped particles are generated by Pickeringemulsions. Alginate capsules containing oil cores may be prepared fromPickering emulsion templates. In some embodiments, pre-gelledCa-alginate nanoparticles may be first formed and used as a solidemulsifier to deposit onto the oil droplets to stabilize the oil inwater (O/W) emulsion. The solvent (which may serve as a second phase)may then be removed to shrink the oil droplets and interlock theCa-alginate nanoparticles present at the interface to form a continuousshell. This technique is expected to produce alginate microcapsules withdiameters of less than 5 micrometers to more than 100 micrometers,depending on the emulsification tool used. A variety of emulsifiers maybe used instead of alginate chains. Another example of such emulsifieris polyglycerol polyricinoleate (PGPR). In some embodiments, a pluralityof emulsifiers may be used. For example, the PGPR and lecithin may beused. In some embodiments, the lecithin and PGPR are used together toreduce the amount of PGPR.

2.4. Immiscible Multi-Phase Particles

FIG. 6 illustrates an example cross-section of a particle 600 with threelayers. Such particles 600 may include a core 601, which containsencapsulants 602, and an interior shell 603, and an exterior shell 604.In some embodiments, the shells 603-4 do not contain any encapsulants.In some embodiments, the shells 603-4 may also contain encapsulants.

In some embodiments, a particle 600 may be formed by O/W/O/W process.The inner oil phase may comprise a first polymer, a first encapsulant(e.g. CBD), and a first surfactant. The inner water phase may comprise asecond polymer, a second surfactant, and a second encapsulant. In someembodiments, the first O/W emulsion may be carried out above the glasstransition temperature of the first and the second polymers.

The outer oil phase may include a third polymer, a third surfactant, anda third encapsulant. In some embodiments, the third polymer may have aglass transition temperature lower than the first and the secondpolymer.

In some embodiments, there is only one droplet of the inner oil phaseinside the inner water phase, similar to particle 600. In someembodiments, multiple droplets of inner oil phase may be inside theinner water phase, similar to particle 700 shown in FIG. 7.

In some embodiments, manufacturing particles may include multiplelayers, such as 2, 3, 4, or 5 layers surrounding the core. In someembodiments, some of these layers may contain a different or similaractive ingredients.

In some embodiments, some of these layers may contain no activeingredients. Such layers may be added to tune the release kinetics orprovide stability for the particle in the surrounding environment (e.g.moisture, fat, pH, temperature, etc.)

In some embodiments, manufacturing particles may include obtaining othertypes of multiple emulsions such aswater-in-oil-in-water-in-oil-in-water (W/O/W/O/W). O/W may includeliquid oil droplets dispersed in a continuous liquid water phase. O/Wmay be formed from two immiscible or nearly immiscible water and oilphases.

FIG. 8 shows a particle with a core 601 and three layers surrounding thecore (603, 604, and 605.) In some embodiments, all the layers of aparticle shown in FIG. 8 may be prepared by emulsification (e.g. aW/O/W/O/W emulsion.) in some embodiments, some of the layers of aparticle shown in FIG. 8 may be prepared by emulsification and some ofthe layers may be prepared by other conventional techniques, e.g., usinga conventional coating pan, an airless spray technique, fluidized bedcoating equipment, or the like. For example, a particle with 3 layerssurrounding a core, similar to FIG. 8, may be manufactured by a O/W/Oemulsification followed by coating the third layer (e.g. layer 605 inFIG. 8) in a fluidized bed coater.

In some embodiments, the polymer chains in water or oil phases may becaused to crosslink or otherwise solidify by controlling thetemperature. In some embodiments, a crosslinking agent may be added tocrosslink the polymer chains. The crosslinking agent may be addeddirectly to the phase containing the polymer chains or indirectly. As anexample of indirect addition, to crosslink polymer chains of sodiumalginate dispersed in water phase, a calcium-containing chemical, suchas calcium stearoyl-2-lactylate (CSL), may be added to the oil phase andduring and after the emulsification, the calcium ions may diffuse to thewater phase and crosslink the alginate chains.

In some embodiments, O/W emulsions may be made by pre-processing the oilphase and water phase with a variety of techniques prior to combination.In some embodiments, the oil phase may be heated to 250° C. prior toemulsification. In some embodiments, the oil phase may be heated to 200°C. prior to emulsification. In some embodiments, the oil phase may beheated to 150° C. prior to emulsification. This may be done to dissolvesurfactants, polymer chains and encapsulants. In some embodiments, thewater phase may be heated to 90° C. prior to emulsification. In someembodiments, the water phase may be heated to 70° C. prior toemulsification. In some embodiments, the water phase may be heated to60° C. prior to emulsification. In some embodiments, the heating process(e.g., to between 60 and 90° C., inclusive) may be done to dissolvesurfactants, and polymer chains. In some embodiments, the heatingprocess may be done to control the viscosity of the oil phase.Temperature ranges may be selected based on the type and amount ofsurfactant, encapsulants, polymer chains, and salts being added to theoil phase and to the water phase. For instance, for some of the typesand amounts of surfactant described below, temperatures outside theseranges are expected to cause either incomplete solubility (ormiscibility) below the low end of the temperature range, or degradationof the chemical structure of the surfactant molecule above the high end,none of which is to suggest that any subject matter is disclaimed,either here or elsewhere in this document.

In some embodiments, hydrophilic-lipophilic balance (HLB) values of themediums (e.g., water or oil phases) may be tuned before the nextemulsion. For example, to perform a W/O emulsion, polyglycerolpolyricinoleate (PGPR) is added to the oil phase in some embodiments.After the W/O emulsion is made, to adjust the HLB value of thecontinuous phase (here oil phase) for the next emulsion (here O/W),lecithin may be added to the continuous phase to increase the HLB valuesuitable for an O/W emulsion.

In some embodiments, to hinder the diffusion of the encapsulant to theouter phases, inner phases may be polymerized. In some embodiments, apolymer is dissolved at a temperature above its glass transitiontemperature and after the emulsion, the temperature may be kept belowthe glass transition temperature to keep that phase solidified. Forexample, ethylcellulose may be dissolved in the oil phase by increasingthe temperature of the oil phase above the glass transition temperatureof ethylcellulose. After the emulsion, the temperature may be kept belowthe glass transition temperature of the ethylcellulose to keep the oilphase in gelled form, in some embodiments.

In some embodiments, a phase may be partially (e.g. 2%, 5%, 10%, 20%,50%, or 80%) polymerized to keep the viscosity low or minimize theamount of polymer being used. For example, in a W/O emulsion, the oilphase may contain ethylcellulose and the temperature may be kept abovethe glass transition temperature during the emulsification. After theW/O emulsification and before the next emulsification (here O/W) thetemperature may be dropped below the glass transition temperature tokeep the W/O in gelled form. Then, the gelled W/O may be mixed with moreoil before the next emulsion to reduce the viscosity in order to achievea proper mixing in the next emulsification step, in accordance with someembodiments.

In some embodiments, different polymers with different glass transitiontemperatures, crosslinking temperatures, or crosslinking agents may beused. For example, for inner oil phases, ethylcellulose with higherglass transition may be used compared to ethylcellulose used for outeroil phases. In this manner, the inner phases may be kept solidifiedwhile the outer oil phases are in a liquid state, which in someembodiments is helpful for proper emulsification.

In some embodiments, the oil phase may be gelled. Gelling agents may below-molecular-weight organogelators such as 12-hydroxystearic, orpolymeric gelators such as ethylcellulose. Ethylcellulose may gel theoil phase, by first being dissolved in the edible oil at temperaturesbetween 120 and 190° C., which is approximately where the glasstransition temperature of ethylcellulose lies. To facilitatedissolution, a plasticizer, such as a food surfactant molecule, may beadded. The type of plasticizer used in the formulation may impact thestorage modulus of the gel formed. Surfactants with small hydrophilichead groups may form stronger gels, which may be due to their moreprominent plasticizing effect. The cooling of the mixture is expected topromote the interaction between the ethylcellulose polymers, inducingthe formation of inter-polymer hydrogen bonds. These interactions maycreate a three-dimensional polymer network that will behave as a trap ofthe liquid oil. The physical gel may be supported by hydrogen bondsformed between the unsubstituted hydroxyl groups of the ethoxylatedglucose units.

In some embodiments, the gel strength is controlled by tuning thecooling rates. Different cooling rates may affect gel strength, highcooling rates being related to a weaker network structure.

In some embodiments, a lipophilic surface active agent, which mayinclude a metal cation, may be used to cause gelation of an aqueoussoluble/gellable polysaccharide, such as sodium alginate. Lipophilicsurface active agents may include C₆-C₂₀ fatty acids including anappropriate metal cation, for example, calcium stearate, calciumpalmitate or other calcium, copper, zinc, potassium (kappa carrageenan)or other metal cation salt of a C₆-C₂₀ fatty acid. The rate ofpolysaccharide gel formation (e.g., complexation with polyvalent metalcations) may be increased by acidifying the polysaccharide containingaqueous solution with vinegar, hydrochloric acid, phosphoric acid, andthe like.

In some embodiments, the external aqueous solution used to form themultiple emulsions may include between about 0.1% and about 5% by weightof a hydrophilic emulsifier. A hydrophilic emulsifier may have an HLB ofat least about 8 or higher.

In some embodiments, the release kinetics of the encapsulant in aproduct (before consumption) or in human or animal digestive tracts(after consumption) may be controlled by the number of water and oillayers encapsulating the encapsulant, the viscosity of these layers, theporosity of the layers, the type of polymers in each layer, and thelevel of crosslinking of polymers at each layer.

In some embodiments, the release of the encapsulant is delayed byincreasing the viscosity of the oil and water phases. In someembodiments, a polymer is added to the oil or water phases to increasethe viscosity. Oil layers may act as barriers for oil-immiscibleencapsulants and water layers may act as barriers for water-immiscibleencapsulants.

In some embodiments, the release kinetics are tuned by controlling thepolymerization degree, crosslinking degree, concentration of thepolymer, viscosity of the polymer, porosity of the polymerizedstructure, and number of water and oil layers encapsulating theencapsulants.

In such embodiments, multi-layered particles may be used for a varietyof reasons, such as prolonging the diffusion of the encapsulants to thesurrounding medium or having different release kinetics for a single ormultiple different types of encapsulants.

In some embodiments, particles may include two or more encapsulants,wherein at least one of the encapsulants increase or complement theeffect of the one of the encapsulants. Such complementary encapsulantsmay be released during the same duration, two separate but overlappingdurations, two non-overlapping durations, or any combination thereof

In some embodiments, particles may include two or more encapsulants,wherein at least one of the encapsulants counteracts or reduces theeffect of the one of the encapsulants. In some embodiments, theencapsulant without the counteracting or reducing effect may be locatedin one or more inner layers or in the core. In this way, a particle mayrelease a first encapsulant from one or more outer layers, followed bythe release of a second encapsulant in the inner layers or core whichcounteracts or reduces the effect of the first encapsulant.

Any combination of encapsulants where the some of the encapsulantscounteracts or reduces the effect of other encapsulants may becontrolled and tuned by using multi-layered particles. Exemplarycombinations include a sleep aid (to induce sleep) and a stimulant suchas caffeine (to wake up a consumer), both being payloads in particleswith staggered release times. For example, 90 wt % a first activeingredient may be released (e.g. in 0.5, 1, 2, 4, or 12 hours) beforemore than 10 wt % a second payload is released.

3. Solid Particles

Some embodiments may be implemented as solid particles that, whenmanufacturing is complete, are not (or are not yet) dispersed in aliquid medium, e.g., as a powder or small beads (mean diameter of 0.4,0.8, 1, 2, 3, 5, 10, 100, 1000, or 2000 microns). In some embodiments,particles may be allowed to rest on an absorbent surface for a period oftime to remove any surface residue therefrom.

In some embodiments, an impermeable shell is coated on the particles toseal the pores and thereafter the particles are dried to have a soliddry outer shell surrounding the encapsulants in the core. In someembodiments, the core is an oil phase. In some embodiments, the core isa solid phase. In some embodiments, the core is a combination ofcomponents mentioned above.

In some embodiments, spray drying devices may be used to dry theparticles and transfer them from liquids state into solid state. In someembodiments, spray drying may include a high-pressure nozzle and acentrifugal force (e.g. an atomizer.) A gas or air may be used for thespray drying, including heated air or hot air at a temperaturesufficient to dry the powder having the desired moisture content (e.g.0.1, 0.5, 1, 2, 5, 10% water content). In some embodiments, the gas isan inert gas such as nitrogen or nitrogen-enriched air.

In some embodiments, a hydrocolloid, such as maltodextrin or gum Arabic,may be added to the external aqueous phase before the spray dryingprocess.

In some embodiments, a fluidized bed may be used to control the moisturecontent of the particles. In some embodiments, a fluidized bed may becoupled with a spray drier to coat a layer (e.g., shellac) on theparticles.

FIG. 9 illustrates an example cross-section of a solid particle 900having a dispersed phase 901, containing an encapsulant 902, and acontinuous phase 903. Such particle may be manufactured using varioustechniques, including emulsification and spray coating. For example, abead 900 may be manufactured using a W/O emulsification, wherein theaqueous phase contains an encapsulant and the oil phase have a polymeror wax. In some embodiments, the polymer has a glass transitiontemperature above room temperature and the emulsification is carried outat elevated temperatures (e.g. 50, 80, or 90° C.). After theemulsification, the temperature is lowered below the glass transitiontemperature of the polymer to immobilize (e.g. solidify) the continuousphase. In some embodiments, the continuous phase may be immobilized bydrying (e.g. fully or partially) a solvent in the continuous phase (e.g.water or organic solvent) or chemical methods (e.g. crosslinking thepolymer in the continuous phase.) In some embodiments, the solidcontinuous phase may be grinded into small beads or a powder.

In some embodiments, an emulsion (e.g. W/O, W/O/W, or O/W/O) may betransformed to a solid phase (e.g. solid chunks or flakes). Thereafter,the solid phase may be grinded into smaller particles (e.g. powder orsmall beads) using various grinding techniques. Such particles may beused as final products or may undergo further processing such asspherification or layer coating.

In some embodiments, solid particles may have multiple layers. In someembodiments, some of these layers may contain a different or similaractive ingredients. In some embodiments, some of these layers maycontain no active ingredients. Such layers may be added to tune therelease kinetics, mask flavor, or provide stability for the particle inthe surrounding environment (e.g. moisture, fat, pH, temperature, etc.)

In some embodiments, a layer is a combination of different materials(e.g. combination of film-forming polymer such as ethyl cellulose, aplasticizer, and a stabilizers) to provide a set of desired properties(e.g. moisture control and controlled release) with a single layer.

In some embodiments, the particle in liquid state (e.g. wet mass) may bepassed through an extruder in order to form an extrudate. Any suitableextruder may be used to extrude the wet mass. Suitable extruders includescrew extruders, screen extruders, gear extruders, cylinder extrudersand radial extruders.

In some embodiments, an extrudate may be unitized in order to formindividual solid-state particles. While having an appropriatecross-sectional size, the extrudate may have a length greater thandesired for the individual particles. Unitizing includes any process bywhich the extrudate is broken down into smaller units that fall withinthe desired size dimensions for the particles. Any unitizing method maybe utilized in order to alter the extrudate into the desired shape forthe particles. In some embodiment where spherical particles are desired,the extrudate may be sent to a spheronizer. Any suitable spheronizer andany suitable operating conditions for the spheronizer may be used.

In some embodiments, solid-state particles may be formed using rotarygranulation techniques, powder layering techniques, spray dryingtechniques, spray chilling techniques, liquid extrusion/coextrusion, 3-DPrinting, concentric nozzles, extrusion/spheronization, and combinationsthereof.

In some embodiments, solid-state particles may be formed using spraydrying techniques. In some embodiments, a mixture containing an activeingredient may be spray dried to form a core. The mixture may beatomized and sprayed into a chamber through a heated air stream. Thiscauses the liquid component of the mixture to evaporate, resulting indried, generally spherical shaped cores. Such cores may be used as finalproduct or may be further processed to coat layers on them.

FIG. 10 illustrates an example cross-section of a solid particle 1000with a dispersed phase 1001, containing an encapsulant 1002, acontinuous phase 1003, and two layers (1004 and 1005) surrounding thecontinuous phase. In some embodiments, all the layers of a particleshown in FIG. 10 may be prepared by emulsification (e.g. a O/W/O/W/Oemulsion.) in some embodiments, some of the layers of a particle shownin FIG. 10 may be prepared by emulsification and some of the layers maybe prepared by other techniques such as spray coating. For example, aparticle similar to FIG. 10, may be manufactured by a W/O emulsificationfollowed by coating the two layers layer (1004 and 1005) usingconventional techniques, e.g., using a conventional coating pan, anairless spray technique, fluidized bed coating equipment, or the like.

With reference to FIG. 11, a method 1100 of preparing a particle, inaccordance with some embodiment, may generally include some of thefollowing steps: a step obtaining various phases as shown in block 10, astep of mixing the phases as shown in block 12, a step of transferringparticles from liquid state to solid phase as shown in block 14, and astep of forming layers as shown in block 16.

In some embodiments, various phases, including aqueous and non-aqueous,may be obtained by combining various ingredients as shown in block 10.Each of these phases may contain encapsulants, polymers, carriersolvents, and other types of ingredients, in accordance with someembodiments.

In some embodiments, after the phases are ready, the phases are mixedtogether, as shown in block 12, to obtain the particles using the mixingtechniques disclosed in some of the embodiments. In some embodiments,particles are formed by a phase transfer as shown in block 14. Forexample, a solid bead may be formed by solidifying a particle dispersedin a solution (e.g. a W/O emulsion.) The liquid state to solid phasetransfer may be carried out by various techniques (e.g. spray drying),in accordance with some embodiments.

In some embodiments, multiple layers may be formed around the particlesby various layering techniques (e.g. powder layering, rotary granulator,or fluidized bed coater), as shown in block 16.

4. Materials

In some embodiments (e.g., any of the expressly described embodiments,which is not to suggest that other references to “some embodiments” donot also pertain to any of the described embodiments), some or all ofthe ingredients, including the particles and the encapsulants, are GRAS(generally recognized as safe). GRAS status is an American Food and DrugAdministration (FDA) designation that a chemical or substance added tofood is considered safe by experts, and so is exempted from the usualFederal Food, Drug, and Cosmetic Act (FFDCA) food additive tolerancerequirements. GRAS include any substance that is added to food, subjectto approval by FDA, unless the substance is generally recognized, amongqualified experts, as having been shown to be safe for its intended use,or unless the use of the substance is excluded from the definition of afood additive. Or the present techniques are also useful innon-food-related use cases, in which case non-food-grade ingredients maybe used.

4.1. Particles

In some embodiments (e.g., any of the expressly described embodiments,which is not to suggest that other references to “some embodiments” donot also pertain to any of the described embodiments), a buffering oilyinterface may be used during a particle formation. It may be formed ofany oily substance, such as oils, liquid fats, fatty acids, or any oilysolution that has a density lower than that of the first or second phasesuch as oleic acid, eicosapentaenoic acid (EPA), and docosahexaenoicacid (DHA). It may also take the form of an oily emulsion. In someembodiments, the buffering oily layer is formed of olive oil, butterfat,coconut oil, palm kernel oil, palm oil, animal fats, castor oil,flaxseed oil, grapeseed oil, soya oil, peanut oil, fish oil, rapeseedoil, glycerol, sorbitol, sucrose, propylene glycol, polyglycerol,sunflower oil or mixtures thereof, where such mixtures have any of theforegoing oils as their base.

In some embodiments, an emulsifier may be used to facilitate theemulsification process. Examples of such emulsifiers include alginicacid, sodium alginate, potassium alginate, ammonium alginate, calciumalginate, propane-1,2-diol alginate, agar, carrageenan, locust bean gum(carob gum), guar gum, tragacanth, gum Acacia, Xanthan gum, sorbitol,mannitol, glycerol, lecithin, pectin, amidated pectin, sodium andpotassium phosphates, sodium and potassium polyphosphates, microcrystalline, methylcellulose, hydroxy propyl cellulose,hydroxypropyl-methylcellulose, ethylmethylcellulose,carboxymethylcellulose, Sodium, potassium, and calcium salts of fattyacids, mono- and di-glycerides of fatty acids, esters of mono- anddi-glycerides of fatty acids, Sucrose esters of fatty acids,sucroglycerides, polyglycerolesters of fatty acids, propane-1,2-diolesters of fatty acids, Sodium Stearoyl-2-lactylate, calciumStearoyl-2-lactylate, and Stearyl tartrate, propylene glycol alginate,polyethylene glycol 400, polysorbates, such as polyoxyethylene sorbitanfatty acid ester (Tween) and Span products, in particular Tween 20, 60,80, rubbers such as gum arabic, pectins, starches and modified starches,such as Purity Gum, or proteins, such as caseinates from milk and anycombination thereof among other emulsifiers. In some other embodiments,other types of emulsifiers such as alginic acid, sodium alginate,potassium alginate, calcium alginate, agar, guar gum, and xanthan gum isused.

In some embodiments, an alginate alkali metal salt may be used. Thealginate alkali metal salt may be formed between alginate anions andalkali metal cations. Examples of suitable alginate alkali metal saltsinclude Sodium alginate and potassium alginate.

In some embodiments, a particle may be made of two different types ofpolymers. A first type of polymer may function as a structural polymer.The particle may further contain at least one secondary polymer thatexhibits greater swelling in water than the first polymer. In variousembodiments, the greater swelling in water is expressed as a highervalue of the Hildebrand solubility parameter. Examples of polymers thatmay serve as the at least one first polymer include polylactic acid,polyglycolic acid, polylactic-co-glycolic acid, polycaprolactone,polyphosphoester, polyvinyl acetate, polystyrene, polyglucosamine,gelatin, and gum arabic. Examples of swellable materials that may serveas the at least one second polymer include polyethylene oxide,polyacrylic acid, polyvinylpyrrolidone, polyvinyl alcohol,polyglucosamine, polyvinyl methyl ether-co-maleic acid, hyaluronic acid,and polysaccharides. Examples of the polysaccharides include gum arabic,alginate, carboxymethyl cellulose, hydroxypropylmethyl cellulose,hydroxyethyl cellulose, starch, and the like.

In some embodiments, when the first liquid contacts with the secondliquid, the multivalent cations of the first liquid will cross-link withpolysaccharides in the second liquid thereby forming coordination bondsto create a solid phase. When the first liquid is dispersed in thesecond liquid, the creation of the solid phase forms capsules with asolid shell encapsulating the first liquid in the core.

In some embodiments, the first liquid may further include a thickeningagent. Examples of suitable thickening agents include polysaccharides,such as xanthan gum, guar gum, starch, or agar agar. A thickening agentmay be 1,3-butylene glycol, Acacia, acetic and fatty acid esters ofglycerol, acetone, acetone peroxides, acetylated distarch adipate,acetylated distarch phosphate, acetylated monoglycerides, acid-treatedstarch, adipic acid, agar, alginic acid, alkaline-treated starch,aluminum ammonium sulfate, aluminum potassium sulfate, aluminumsilicate, aluminum sodium sulfate, aluminum sulfate, aluminum ammoniumsulfate, ammonium adipate, ammonium alginate, ammonium bicarbonate,ammonium carbonate, ammonium chloride, ammonium dihydrogen phosphate,ammonium hydrogen carbonate, ammonium phosphate, ammonium phosphatides,ammonium salts of phosphatidic acid, ammonium sulfate, anoxomer,ascorbic acid, ascorbyl palmitate, ascorbyl stearate, azodicarbonamide,beeswax, benzoic acid, benzoyl peroxide, beta-cyclodextrin, bleachedstarch, bone phosphate, brominated vegetable oil, butylp-hydroxybenzoate, butylated hydroxyanisole, butylatedhydroxymethylphenol, butylated hydroxytoluene, calcium acetate, calciumalginate, calcium aluminum silicate, calcium ascorbate, calciumbenzoate, calcium bromate, calcium carbonates, calcium chloride, calciumcitrate, calcium dihydrogen phosphate, calcium disodiumethylenediamine-tetraacetate, calcium DL-malate, calcium ferrocyanide,calcium gluconate, calcium hydrogen sulfite, calcium hydroxide, calciumiodate, calcium lactate, calcium lactobionate, calcium peroxide, calciumphosphate, calcium polyphosphates, calcium propionate, calciumpyrophosphatecalcium salts of fatty acids, calcium silicate, calciumsorbate, calcium stearate, calcium stearoyl lactylate, calcium sulfate,calcium tartrate, calciumiodiate, candelilla wax, carbamide, carbondioxide, carnauba wax, carob bean gum, carrageenan, castor oil,cellulose gum, celluloses, chlorine, chlorine dioxide, cholic acid,choline salts and esters, citric acid, citric and fatty acid esters ofglycerol, crosslinked sodium carboxymethylcellulose, cupric sulfate,D-alpha-tocopherol, dammar gum, decanoic acid, dedesoxycholic acid,dedextrins, dextrin ethyl cellulose, dehydroacetic acid, dextrose,diacetyltartaric acid esters of mono- and diglycerides of fatty acids,diammonium hydrogen phosphate, dicalcium pyrophosphate, diethylpyrocarbonate, dilauryl thiodipropionate, dimethyl dicaronate,dimethylpolysiloxane, dioctyl sodium sulfosuccinate, dipotassiumhydrogen phosphate, disodium ethylenediamine-tetraacetate, disodiumhydrogen phosphate, disodium pyrophosphate, distarch phosphate,DL-alpha-tocopherol, DL-tartaric acid, dodecyl gallate, erythorbic acid,ethoxyquin, ethyl alcohol, ethyl cellulose, ethyl hydroxyethylcellulose, ethyl p-hydroxybenzoate, ethyl protocatechuate, ethylenedichloride, esters of glycerol and thermally oxidized soy bean fattyacids, ethoxylated mono- and diglycerides, ethyl hydroxyethyl cellulose,ferric ammonium citrate, ferrous ammonium citrate, formic acid, gellangum, gelatin, genipin, gibberellic acid, glucono delta-lactone,glycerin, glycerol, glycerol ester of wood rosin, guaiac resin, guargum, gum Acacia, gum arabic, gum ghatti, gum guaiac, heptylparaben,peroxide derivatives, hydrogen peroxide, hydroxylated lecithin,hydroxypropyl cellulose, hydroxypropyl distarch phosphate,hydroxypropylmethyl cellulose, amino methacrylate, hydroxypropyl starch,insoluble polyvinylpyrrolidone, iron gluconate, iron lactate, isoamylgallate, isopropyl alcohol, isopropyl citrate mixture, kaolin, karayagum, L(+)-tartaric acid, lactated monodiglycerides, lactic and fattyacid esters of glycerol, lactitol, lactylated fatty acid esters ofglycerol and propylene glycol, lactylic esters of fatty acids, lauricacid, lecithin, locust bean gum, magnesium carbonate, magnesiumDL-lactate, magnesium gluconate, magnesium hydrogen carbonate, magnesiumhydroxide, magnesium hydroxide carbonate, magnesium L-lactate, magnesiumoxide, magnesium salts of fatty acids, magnesium silicate, magnesiumstearate, maltitol, mannitol, methyl alcohol, methyl ethyl cellulose,methylcellulose, methylene chloride, metatartaric acid, methylparaben,microcrystalline cellulose, milk protein, mineral oil, modifiedcellulose, modified starches, monoglyceride citrate, mono- anddiglycerides, monostarch phosphate, myristic acid, nisin, nitrogen,nitrous oxide, nordihydroguaiaretic acid, o-phenylphenol, octanoic acid,octyl gallate, oleic acid, oxidized starch, oxystearin, palmitic acid,paraffin wax, pectin, pentapotassium triphosphate, pentasodiumtriphosphate, petrolatum, petroleum jelly, petroleum wax, phosphated distarch phosphate, phosphoric acid, pimaricin, poloxamer 33 1, poloxamer407, polydimethylsiloxane, polydextroses, polyethylene glycols,polyglycerol esters of fatty acids, polyoxyethylenes, polypropyleneglycol, polysorbates, polyvinylpolypyrrolidone, polyvinylpyrrolidone,potassium acetate, potassium acid tartrate, potassium adipate, potassiumalginate, potassium benzoate, potassium bicarbonate, potassiumcarbonate, potassium chloride, potassium citrate, potassium dihydrogencitrate, potassium dihydrogen phosphate, potassium ferrocyanide,potassium gibberellate, potassium gluconate, potassium hydroxide,potassium iodate, potassium lactate, potassium metabisulfite, potassiumnitrate, potassium nitrite, potassium persulfate, potassium phosphate,potassium polymetaphosphate, potassium polyphosphates, potassiumL(+)-tartrate, potassium salts of fatty acids, potassium sorbate,potassium sulfate, potassium sulfite, potassium tripolyphosphate,processed eucheuma seaweed, propane-1,2-diol alginate, propionic acid,propyl gallate, propyl p-hydoxybenzoate, propylene glycol, propyleneglycol alginate, propylene glycol esters of fatty acids, propyleneglycol mono- and diesters, propylene oxide, propylparaben, quillaiaextracts, rice bran wax, salts of fatty acids, shellac, silicon dioxide,sodium acetate, sodium acid, sodium acid pyrophosphate, sodium adipate,sodium alginate, sodium aluminosilicate, sodium aluminum phosphate,sodium ascorbate, sodium benzoate, sodium bicarbonate, sodium bisulfate,sodium carbonate, sodium carboxymethylcellulose, sodium caseinate,sodium chloride, sodium citrate, sodium dehydroacetate, sodiumdiacetate, sodium dihydrogen citrate, sodium dihydrogen phosphate,sodium dioxide, sodium DLmalate, sodium erythorbate, sodiumferrocyanide, sodium fumarate, sodium gluconate, sodium hydrogencarbonate, sodium hydrogem DL-malate, sodium hydrogen sulfite, sodiumhydroxide, sodium hypophosphite, sodium L(+)-tartrate, sodium lactate,sodium lauryl sulfate, sodium metabisulfite, sodium metaphosphate,sodium nitrate, sodium nitrite, sodium phosphates, sodium polyacrylate,sodium polyphosphates, sodium potassium tartrate, sodium propionate,sodium pyrophosphate, sodium salts of fatty acids, sodiumsesquicarbonate, sodium stearoyl lactylate, sodium stearyl fumarate,sodium sulfite, sodium tartrate, sodium thiosulfate, sodiumtripolyphosphate, sorbic acid, sorbitan monolaurate, sorbitanmonooleate, sorbitan monopalmitate, sorbitan monostearate, sorbitantristearate, sorbitol, sorbitol sodium, sulfur dioxide, stannouschloride, starches, starch acetate, starch sodium octenylsuccinate,stearic acid, stearyl citrate, stearyl monoglyceridyl citrate, stearyltartrate, succinic acid, succinylated monoglycerides, sucroglycerides,sucroses, sucrose acetate isobutyrate, sucrose esters of fatty acids,talc, tannic acid, tannins, tara gum, tartaric acid,tert-butylhydroquinone, tetrapotassium pyrophosphate, tetrasodiumpyrophosphate, thiodipropionic acid, tocopherols, tragacanth, tragacanthgum, triacetin, triammonium citrate, tricalcium phosphate,trichloroethylene, triethyl citrate, trimagnesium phosphate,tripolyphosphate, tripotassium citrate, tripotassium phosphate,trisodium citrate, trisodium phosphate, urea, waxes, xanthan gum,xylitol, derivatives thereof, and combinations thereof. The thickeningagent may be a polysaccharide. The thickening agent may be selected fromxanthan gum and a galactomannan (e.g., locust bean gum, guar gum,combinations thereof, or derivatives thereof.)

In some embodiments, the gelatin shells may contain a preservative, suchas mixed parabens, for example, methyl or propyl parabens. The parabensare incorporated into the shell formulation in minor proportions (e.g.0.1, 0.5, 1, 2, 5 wt %) as compared to the total weight of the shellformulation.

In some embodiments, particles may have a gelatin shell. In someembodiments, the addition of partial glycerides of fatty acids enableencapsulating ethanol without damaging the mechanical stability of thegelatin shell. The partial glycerides useful in the fill includemonoglycerides or diglycerides as well as mixtures thereof. Suitablecommercially available products include, for example, glycerolmonocaprylate (Imwitor 308 of Dynamit Nobel), glycerol monodicaprylate(Imwitor 908), mixtures comprising glycerol monodicaprylate and glycerolmonodicaprate (Imwitor 742) and partial glycerides of ricinoleic acid(Softigen 701 and Rilanit).

In some embodiments, a particle may be made from capsule formingmaterials comprising gelatin. Various gelatins may be used for thispurpose. Some embodiments may us gelatin having a viscosity of 1 to 30millipoises and a bloom strength up to 150 grams or gelatin having abloom value of 160 to 250. Gelatin has the advantage as an encapsulatingmaterial in that it is heat-moldable. The gelatin capsule size and shapemay vary depending on the amount of fill that will be contained therein.The capsule shell material may be used to form a wide variety of shapesand sizes such as spheres, oblong shapes, disks, squares, cylindrical,and shapes that resemble the appearance of a garnish associated with analcoholic beverage.

In some embodiments, a lipophilic solvent or suspension carrier may beselected from a group consisting of short-chain triglycerides (SCTs),medium-chain triglycerides (MCTs), long-chain triglycerides (LCTs),medium-chain partial glycerides, polyoxyethylated fatty alcohols,polyoxyethylated fatty acids, polyoxyethylated fatty acid triglyceridesor partial glyceride, ester of fatty acids with low molecular weightalcohols, a partial ester of sorbitan with fatty acids, apolyoxyethylated partial ester of sorbitan with fatty acids, a partialester of sugars or oligomeric sugars with fatty acids, a polyethyleneglycol, vegetable oil, and any combination thereof.

In some embodiments, the carrier oil may be selected from the groupconsisting of Cannabis oil, borage oil, coconut oil, cottonseed oil,soybean oil, safflower oil, sunflower oil, castor oil, corn oil, oliveoil, palm oil, peanut oil, almond oil, sesame oil, rapeseed oil,peppermint oil, poppy seed oil, canola oil, palm kernel oil,hydrogenated soybean oil, hydrogenated vegetable oils, glyceryl estersof fatty acids, glyceryl behenate, glyceryl distearate, glycerylisostearate, glyceryl laurate, glyceryl monooleate, glycerylmonolinoleate, glyceryl palmitate, glyceryl palmitostearate, glycerylricinoleate, glyceryl stearate, polyglyceryl 10-oleate, polyglyceryl3-oleate, polyglyceryl 4-oleate, polyglyceryl 10-tetralinoleate, behenicacid, caprylic/capric glycerides, and any combination thereof.

In some embodiments, the oil phase may have various components. In somecases, the component (e.g., more than or equal to half by weight orvolume) of the oil phase is a carrier oil, which may be food-grade. Insome embodiments, the carrier oil may not affect (e.g., adversely)consumer-perceivable dimensions product quality (such as appearance,taste, texture, or stability). In some embodiments the carrier oil mayhave ingredients that protect the emulsion from chemical degradationduring storage or itself serve to protect from chemical degradationduring storage. In some embodiments, the carrier oil may increasebioavailability of the emulsion after ingestion. In some embodiments,carrier oils may be beneficial in stabilizing the emulsion from Ostwaldripening, which is a major de-stabilization mechanism in many nano- andmicro-emulsions. As mentioned, Ostwald ripening is a process in whichvery finer droplets of emulsion dissolve into continuous phase and,then, diffuse and redeposit upon larger droplets, thus increasing theaverage size of emulsion droplets. Ostwald ripening occurs because ofthe increased solubility of the dispersed phase (e.g., oil) into theaqueous phase. In some embodiments, this issue may be mitigated (orfully solved) by the introduction of hydrophobic properties into thedispersed phase. In some cases, a single carrier oil may be used, or insome cases, multiple carrier oils may be used (e.g., one correspondingto cannabidiol (CBD) oil and another to convey various vitamins).

In some embodiments, MCT-based oils are expected to afford certainadvantages, as the rate and extent of lipid digestion is believed to behigher for MCT-based oils than LCT-based oils. This effect may beattributed to differences in the water dispersibility of medium and longchain fatty acids formed during lipolysis. Embodiments are not limitedto systems that afford these benefits, though, which is not to suggestthat any other description is limiting.

In some embodiments, LCT-based oils are expected to afford certainadvantages, as the bio-accessibility of bioactive materials may behigher for LCT-based emulsions. This may be attributed to the greatersolubilization capacity of mixed micelles formed from long-chain fattyacids, as these micelles are expected to easily accommodate lipophilicmolecules. Bio-accessibility (or interchangeably, bio-accessibility) canbe quantified by the fraction of the administered dose of theencapsulant that reaches systematic circulation. In some embodiments,where the nature of the encapsulant is unchanged, bioavailability may bedetermined by measuring the total amount of encapsulant excreted after asingle dose. In some other embodiments, bioavailability may be assessedby determining the area under the plasma concentration-time curve.Embodiments are not limited to systems that afford these benefits,though, which is not to suggest that any other description is limiting.

In some embodiments, where the bioactive is THC (C21H30) or similar,LCT-based oils are expected to afford certain advantages. Highlylipophilic drugs are believed to have higher bio-accessibility whenadministered with LCTs rather than MCTs. LCTs contain relativelylong-chain fatty-acids (between 12-20 carbon atoms), which may formmixed micelles with hydrophobic cores long enough to accommodatebioactives. Embodiments are not limited to systems that afford thesebenefits, though, which is not to suggest that any other description islimiting.

In some embodiments, LCT-based oils are expected to afford certainadvantages, as MCTs contain fatty acid chains that are short (6-12carbon atoms), resulting in mixed micelles from its digestion productsthat are too small to accommodate certain bioactives, such as Cannabis.However, MCTs are expected to have about two orders of magnitude highersolubility than LCTs, as MCTs esterified with glycerol. Embodiments arenot limited to systems that afford these benefits, though, which is notto suggest that any other description is limiting.

In some embodiments, medium-long-chain triglycerides (MLCTs) may be usedas a resolution in choosing between carrier oils. MLCTs contain bothmedium- and long-chain fatty acids.

In some embodiments, where oils with high interfacial tension,viscosity, and hydrophobicity are required, MCT- and LCT-based oils maybe used. These oils may be used in high-energy emulsification methods.Droplets created by MCT- and LCT-oils are considered to be lessefficient for producing droplets with small particle size; however,these oils are expected to produce stable droplets as their large molarvolume renders them insoluble in water.

In some embodiments, where emulsion stability is to be increased (e.g.,optimized), SCT- and MCT-oils may be used.

In some embodiments, a weighting agent can include ester gum, brominatedvegetable oil, sucrose acetate isobutyrate. In some embodiments, theamount of a weighting agent is selected based on the desired targetdensity of the resulting oil phase.

In some embodiments, polyethylene oxide may be used to control therelease kinetics by partially or fully melting the polyethylene oxidedispersed in a particle.

In some embodiments, a wax or a combination of different types of waxesmay be used to control the release kinetics. The term wax is intended toinclude, but not be limited to, bees wax, rice bran wax, camauba wax,candelilla wax, carnauba wax, glycerol monostearate, glycerol oleate,spermaceti, and the like.

In some embodiments, a particle may be solidified by cross-linking thealginate polymer chains with divalent cations. Divalent cations arebelieved to bind to the guluronate blocks of the alginate polymerchains, forming an ‘egg-box’ structure. Alginate displays varyingaffinities toward different cations; the degree of affinity of alginatetoward the following cations decreases as Pb>Cu>Cd>Ba>Sr>Ca>Co, Ni,Zn>Mn (each being an abbreviation of an element in the periodic table).However, in some embodiments, calcium (Ca²⁺) is used for ionotropicgelation of alginate because of its non-toxicity compared with othercations. Among the available calcium sources, calcium chloride (CaCl₂)is often a suitable salt for gelation. CaCl₂ is readily soluble inwater, and thus calcium ions in solution may cross-link with alginatedroplets instantaneously to form hydrogel particles. In someembodiments, insoluble calcium salts, e.g., calcium carbonate (CaCO₃),is used when gradual or controlled cross-linking is desired. Thecross-linking process may be initiated by reducing the pH to dissociatethe insoluble calcium salt. Readily soluble calcium salts, e.g., CaCl₂,may cause spontaneous gelation and are therefore used to preparealginate particles via external, inverse, or multi-step interruptedgelation mechanisms. The use of partially soluble calcium salts, e.g.calcium sulfate (CaSO₄), is expected to allow for slow dissociation ofCa²⁺; however, controlling the gelation kinetics is expected to bedifficult (which is not to suggest that this approach is disclaimed).

In some embodiments, insoluble calcium salts (e.g., CaCO₃) are used toprepare alginate particles through internal gelation mechanism. In someembodiments, the salt is first dispersed in the alginate solution beforeemulsification. Upon emulsification, the gelation process may beinitiated by solubilizing the salt, thus liberating Ca′ forcross-linking with the local alginate polymer chains. Liberation of thesalt may be initiated by reducing the pH using a gelling initiator suchas the introduction of an acid or UV irradiation in the case of aphoto-acid generator. Generally, the pH is reduced by adding acid, suchas glacial acetic acid, to an emulsion. A more gradual gelation may beachieved by pre-adding the glucono delta-lactone to the alginatesolution containing the insoluble salt, where it slowly dissociates thesalt.

In some embodiments, various polyvalent metallic cations may be used topolymerize the sodium alginate chains, including iron, silver,strontium, aluminum, manganese, selenium and, in particular, a calcium,copper or zinc salt (e.g. calcium chloride, calcium lactate, calciumgluconate, calcium carbonate), copper or zinc acetate, sulfate, chlorideor gluconate (e.g. zinc sulphate).

In some embodiments, when the sodium alginate is used, it is difficultor impossible to produce small droplets due to high density andviscosity of these solutions, and in some cases a thickener is addedwith calcium ions to prevent the solution rich in calcium ions fromfloating.

In some embodiments, a small, soft, solid-walled particle may be usedcontaining within an enclosed cavity mainly ethanol. Alginate may beused as encapsulating material because it is highly water soluble, butis insoluble in ethanol and ethanol/water mixtures. In some embodiments,the ethanol contained within the cavity formed by the gelatin, alginateor like material may be pure, substantially pure, or relatively diluteethanol, for addition to and dissolution in an aqueous solution, such asa fruit juice, soft drink (e.g. any commercially available mixer, soda,or the like), or in water. In some other embodiments, the alcohol may bemixed with water, syrup, gel, flavoring or the like.

In some embodiments, various excipients may be incorporated in, or addedto, the particles to provide structure and form to the particles. Theseexcipients may include, but are not limited to (which is not to suggestthat other lists are limiting), carbohydrates including monosaccharides,disaccharides and polysaccharides. For example, monosaccharides such as,dextrose (anhydrous and monohydrate), galactose, mannitol, D-mannose,sorbitol, sorbose and the like; disaccharides such as, lactose, maltose,sucrose, trehalose, and the like; trisaccharides such as, raffinose andthe like; and other carbohydrates such as, starches(hydroxyethylstarch), cyclodextrins and maltodextrins.

In some embodiments, a stabilizing agent is added to the exterior waterphase to stabilize the particles. Examples of such stabilizers aresmall-molecule surfactants such as Tween 20, Span 80, dioctyl sodiumsulfosuccinate, and lecithin, hydrocolloids such as gum arabic, andgelatin, and milk proteins such as whey protein isolate, and sodiumcaseinate. In some embodiments, the stabilization of the particles inthe exterior water phase may be achieved by the Pickering mechanismusing chemicals such as hydrophobically modified starch granules orkafirin protein nanoparticles. In some embodiments, the particles arestabilized in the exterior water phase using mixed biopolymers. Forexample, the particles can be stabilized using complex coacervates ofgelatin with gum arabic, soluble complexes of whey protein withcarboxymethylcellulose sodium (CMC), or multilayers of whey protein withpectin or chitosan with CMC. In some embodiments, the retention of theencapsulated components inside the particles are prolonged by chemicalcomplexation of the encapsulated components within the interior waterphase. For example, the chelation of zinc or magnesium ions by phosvitinor gluconate may be used in the interior water phase to prolong theretention of the encapsulated components.

In some embodiments, pH adjusting agents, such as those selected fromthe group consisting of disodium hydrogen phosphate, sodium acetate,sodium bicarbonate, sodium phosphate tribasic, dipotassium hydrogenphosphate, phosphoric acid, acetic acid, lactic acid, fumaric acid,adipic acid, malic acid, tartaric acid, citric acid, hydrochloric acid,sulfuric acid, salts thereof, and any combination thereof may, be usedto adjust the pH to a value between 2 and

7.5.4.2. Encapsulants

In some embodiments, encapsulants (e.g., active ingredients) areselected from those generally used to enhance physical performance, suchas nootropics, functional ingredients, stimulants, electrolytes,vitamins (e.g. vitamin D3 from lanolin or lichen), proteins, andminerals. Exemplary encapsulants may include, but are not limited to,nutraceuticals, vitamins, supplements, minerals, enzymes, probiotics,bronchodilators, anabolic steroids, analeptics, analgesics, proteins,peptides, antibodies, vaccines, anesthetics, antacids, antihelmintics,anti-arrthymics, antibiotics, anticoagulants, anticolonergics,anticonvulsants, antidepressants, antidiabetics, antidiarrheals,anti-emetics, anti-epileptics, antihistamines, antihormones,antihypertensives, anti-inflammatories, antimuscarinics, antimycotics,antineoplastics, anti-obesity drugs, antiprotozoals, antipsychotics,anti spasmotics, anti-thrombics, antithyroid drugs, antitussives,antiviral s, anxiolytics, astringents, beta-adrenergic receptor blockingdrugs, bile acids, bronchospasmolytic drugs, calcium channel blockers,cardiac glycosides, contraceptives, corticosteriods, diagnostics,digestives, probiotics, diuretics, dopaminergics, electrolytes, emetics,haemostatic drugs, hormones, hormone replacement therapy drugs,hypnotics, hypoglycemic drugs, immunosuppressants, impotence drugs,laxatives, lipid regulators, muscle relaxants, pain relievers,parasympathicolytics, parasympathicomimetics, prostagladins,psychostimulants, sedatives, sex steroids, spasmolytics, sulfonamides,sympathicolytics, sympathicomimetics, sympathomimetics, thyreomimetics,thyreostatic drugs, vasodialators, and xanthines; drugs or medicaments,breath fresheners, vitamins and other dietary supplements, minerals,caffeine, theacrine, Cannabis, nicotine, fruit juices, and the like, andmixtures thereof. Examples of useful drugs include ace-inhibitors,antianginal drugs, anti-arrhythmias, anti-asthmatics,anti-cholesterolemics, analgesics, anesthetics, anti-convulsants,anti-depressants, anti-diabetic agents, anti-diarrhea preparations,antidotes, anti-histamines, anti-hypertensive drugs, anti-inflammatoryagents, anti-lipid agents, anti-manics, anti-nauseants, anti-strokeagents, anti-thyroid preparations, anti-tumor drugs, anti-viral agents,acne drugs, alkaloids, amino acid preparations, anti-tussives,anti-uricemic drugs, anti-viral drugs, anabolic preparations, systemicand non-systemic anti-infective agents, anti-neoplastics,anti-parkinsonian agents, anti-rheumatic agents, appetite stimulants,biological response modifiers, blood modifiers, bone metabolismregulators, cardiovascular agents, central nervous system stimulates,cholinesterase inhibitors, contraceptives, decongestants, dietarysupplements, dopamine receptor agonists, endometriosis managementagents, enzymes, erectile dysfunction therapies such as sildenafilcitrate, which is currently marketed as Viagra™, fertility agents,gastrointestinal agents, homeopathic remedies, hormones, hypercalcemiaand hypocalcemia management agents, immunomodulators,immunosuppressives, migraine preparations, motion sickness treatments,muscle relaxants, obesity management agents, osteoporosis preparations,oxytocics, parasympatholytics, parasympathomimetics, prostaglandins,psychotherapeutic agents, respiratory agents, sedatives, smokingcessation aids such as bromocryptine or nicotine, sympatholytics, tremorpreparations, urinary tract agents, vasodilators, laxatives, antacids,ion exchange resins, anti-pyretics, appetite suppressants, expectorants,anti-anxiety agents, anti-ulcer agents, anti-inflammatory substances,coronary dilators, cerebral dilators, peripheral vasodilators,psycho-tropics, stimulants, anti-hypertensive drugs, vasoconstrictors,migraine treatments, antibiotics, tranquilizers, anti-psychotics,anti-tumor drugs, anti-coagulants, anti-thrombotic drugs, hypnotics,anti-emetics, anti-nauseants, anti-convulsants, neuromuscular drugs,hyper- and hypo-glycemic agents, thyroid and anti-thyroid preparations,diuretics, anti-spasmodics, terine relaxants, anti-obesity drugs,erythropoietic drugs, anti-asthmatics, cough suppressants, mucolytics,DNA and genetic modifying drugs, Cannabis, THC, CBD, and combinationsthereof.

In some embodiments, encapsulants may be a liquid food product selectedfrom cannabidiol (CBD), alcohol, proteins, infusions, vinegars, or anyaqueous or non-aqueous substance in liquid state or resulting from theextraction of any type of solid whose juice has a aqueous content.Additionally, medicines, especially medication for children, may be madeinto micro/nano capsules to make the medicine appear more palatable to achild.

In some other embodiments, other types of oil are used separately or incombination with CBD. Examples of such oils include borage oil, coconutoil, cottonseed oil, soybean oil, safflower oil, sunflower oil, castoroil, corn oil, olive oil, palm oil, peanut oil, almond oil, sesame oil,rapeseed oil, peppermint oil, poppy seed oil, canola oil, palm kerneloil, hydrogenated soybean oil, hydrogenated vegetable oils, glycerylesters of saturated fatty acids, glyceryl behenate, glyceryl distearate,glyceryl isostearate, glyceryl laurate, glyceryl monooleate, glyceryl,monolinoleate, glyceryl palmitate, glyceryl palmitostearate, glycerylricinoleate, glyceryl stearate, polyglyceryl 10-oleate, polyglyceryl3-oleate, polyglyceryl 4-oleate, polyglyceryl 10-tetralinoleate, behenicacid, caprylyic/capric glycerides and any combination thereof.

In some embodiments, one or more herbal ingredients are amongst theencapsulants. Herbal ingredients may include but are not limited to:maca, he shou wu, iporuru (Alchornea castaneifolia), kanna (SceletiumTortosum), honokiol (Magnolia grandiflora), Sour Jujube Seed Semen(Ziziphi Spinosae), Cnidium Fruit (Fructus Cnidii), Corydalis Rhizome(Corydalis yanhusuo), Albizia Bark or Flower (Cortex albiziae), Ginseng(Panax ginseng), Polygonum (Polygoni Multiflori), Fu ling (Poria cocos),CornusFruit (Fructus corni), Chinese Yam (Rhizoma dioscoreae), Muirapuama, Dendrobium sp., Licorice Root Radix (Glycyrrhizae Preparata),Cordyceps (Cordyceps sinensis), Chinese Angelica Root (AngelicaeSinensis), Kratom (Mitragyna speciosa), Bacopa monnieri, Catuaba,Ashwaghanda, Peganum harmala, Wheat Grass, Alfalfa Grass, Oat Grass,Kamut Grass, Echinacea, Chlorella, Amla Fruit, Stinging Nettles, Carob,Mesquite, Chuchuhuasai, Clavo Huasca, Chanca Piedra, Guayusa Powder,Rhodiola rosea, Shilajit, Higenamine, Moringa (Moringa oleifera), HornyGoat Weed (Epidmedium), Astragalus, Aloe Vera, Turmeric, Pine Pollen,Cucurmine (tumeric compound), Hops, Xanthohumol (hops compound), PassionFlower, Mucuna Puriens, Tusli, Black Pepper, Bioperine (black peppercompound), Siberian Ginseng, American Ginseng, Yerba Mate, Lemon Balm,Astragulus, Kava Kava, Schizandra, Skullcap, Valerian, Calif. Poppy,Epidmedium, Pau D'Arco, Gingko, Blue Lotus, White Lilly, and Cacao.Herbal ingredients may comprise essential oils. Exemplary essential oilsinclude but are not limited to: Linalool; B-Caryophyllene; B-Myrcene;D-Limonene; Humulene; a-Pinene; Ylang Ylang (Cananga odorata); Yarrow(Achillea millefolium); Violet (Viola odorata); Vetiver (Vetiveriazizanoides); Vanilla (Vanilla plantifolia); Tuberose (Polianthestuberosa); Thyme (Thymus vulgaris L.); Tea Tree (Melaleucaalternifolia); Tangerine (Citrus reticulata); Spruce, Black (Piceamariana); Spruce (Tsuga Canadensis); Spikenard (Nardostachys jatamansi);Spearmint (Mentha spicata); Sandalwood (Santalum spicatum); Rosewood(Aniba rosaeodora); Rosemary Verbenone (Rosmarinus officinalis);Rosemary (Rosmarinus officinalis); Rose (Rosa damascena); Rose Geranium(Pelargonium roseum); Ravensara (Ravensara aromatica); Plai (Zingibercassumunar) Pine Needle (Pinus sylvestris L.) Petitgrain (Citrusaurantium); Peppermint (Mentha piperita); Pepper, Black (Piper nigrumL.); Patchouli (Pogostemon cablin); Palo Santo (Bursera graveolens);Palmarosa (Cymbopogon martini); Osmanthus (Osmanthus fragrans); Oregano(Origanum vulgare); Orange, Sweet (Citrus sinensis); Oak Moss (Everniaprunastri); Nutmeg (Myristica fragrans) Niaouli (Melaleucaviridifloria); Neroli (aka Orange Blossom) (Citrus aurantium); Myrtle(Myrtus communis); Myrrh (Commiphora myrrha); Mimosa (Acacia decurrens);Melissa (Melissa officinalis L.); Marjoram, Sweet (Origanum majorana);Manuka (Leptospermum scoparium); Mandarin, Red (Citrus deliciosa);Mandarin (Citrus deliciosa); Lotus, White (Nelumbo nucifera); Lotus,Pink (Nelumbo nucifera); Lotus, Blue (Nelumbo nucifera); Lime (Citrusaurantifolia); Lily (Lilum aurantum); Lemongrass (Cymbopogon citratus);Lemon (Citrus limonum); Lavender (Lavandula angustifolium); Lavandin(Lavandula hybrida grosso); Kanuka (Kunzea ericoides); Juniper Berry(Juniperus cummunis); Jasmine (Jasminum officinale); Jasmine Abs(Jasminum sambac); Helichrysum (Helichrysum italicum); Grapefruit, White(Citrus×paradisi); Grapefruit, Pink (Citrus paradisi); Ginger (Zingiberofficinalis); Geranium (Pelargonium graveolens); Geranium, Bourbon(Pelargonium graveolens, 'Herit); Gardenia (Gardenia jasminoides);Galbanum (Ferula galbaniflua); Frankincense (Boswellia carterii);Frangipani (Plumeria alba); Fir Needle White (Abies alba); Fir NeedleSiberia (Abies siberica); Fir Needle Canada (Abies balsamea); Fennel,Sweet (Foeniculum vulgare); Eucalyptus Smithii. Eucalyptus Radiata,Eucalyptus Globulus, Eucalyptus Citriodora, Eucalyptus Blue Mallee(Eucalyptus polybractea); Elemi (Canarium luzonicum); Dill (Anethumgraveolens); Cypress (Cupressus sempervirens); Cumin (Cuminum cyminum);Coriander (Coriandum sativum); Cocoa (Theobroma cacao); Clove (Eugeniacaryophylatta); Clary Sage (Salvia sclarea); Cistus (aka Labdanum)(Cistus ladaniferus L.); Cinnamon (Cinnamomum zeylanicum); Chamomile,Roman (Anthemis nobilis); Chamomile, Blue (Matricaria chamomilla);Celery Seed (Apium graveolins); Cedarwood, Western Red (Thuja plicata);Cedarwood, Blood (Juniperus virginiana); Cedarwood Atlas (Cedrusatlantica); Carrot Seed (Daucus carota); Cardamon (Elettariacardamomum); Caraway Seed (Carum carvi); Cajeput (Melaleuca cajuputi);Cade (Juniperus oxycedrus); Birch, White (Betula alba); Birch, Sweet(Betula lenta); Bergamot (Citrus bergamia); Bay Laurel (Laurus nobilis);Basil (Ocimum basilicum); Basil, Holy (Ocimum sanctum); Basil (Ocimumbasilicum); Balsam Poplar (Populus balsamifera); Balsam Peru (Myroxylonbalsamum); Angelica (Angelica archangelica L.); and combinationsthereof.

In some embodiments, cannabinoids may be among the encapsulants.Cannabinoids include but are not limited to cannabigerol-type (CBG),cannabigerolic acid (CBGA), cannabigerolic acid monomethylether (CBGAM),cannabigerol monomethyl ether (CBGM), cannabichromene-type (CBC),cannabichromanon (CBCN), cannabichromenic acid (CBCA),cannabichromevarin-type (CBCV), cannabichromevarinic acid (CBCVA),cannabidiol-type (CBD), tetrahydrocannabinol-type (THC),iso-tetrahydrocannabinol-type (iso-THC), cannabinol-type (CBN),cannabinolic acid (CBNA), cannabinol methylether (CBNM), cannabinol-C4(CBN-C4), cannabinol-C2 (CBN-C2), cannabiorcol (CBN-C1), cannabinodiol(CBND), cannabielsoin-type (CBE), cannabielsoic acid A (CBEA-A),cannabielsoic acid B (CBEA-B), cannabicyclol-type (CBL), cannabicyclolicacid (CBLA), cannabicyclovarin (CBLV), cannabicitran-type (CBT),cannabitriol, cannabitriolvarin (CBTV), ethoxy-cannabitiolvarin (CBTVE),cannabivarin-type (CBV), cannabinodivarin (CBVD),tetrahydrocannabivarin-type (THCV), cannabidivarin-type (CBDV),cannabigerovarin-type (CBGV), cannabigerovarinic acid (CBGVA),cannabifuran (CBF), dehydrocannabifuran (DCBF), and cannabiripsol (CBR)cannabinoids.

Cannabinoids used in compositions of the present disclosure may bederived from various sources, including but not limited to hemp (e.g.hemp stalk, hemp stem, hemp seed), Cannabis (e.g., Cannabis flower,Cannabis leaf, Cannabis stalk, Cannabis stem, Cannabis seed), Echinaceapurpurea, Echinacea angustifolia, Echinacea pallida, Acmella oleracea,Helichrysum umbraculigerum, Radula marginata, kava, black truffle,Syzygium aromaticum (cloves), Rosmarinus oficinalis, basil, oregano,black pepper, lavender, true cinnamon, malabathrum, Cananga odorata,Copaifera spp., and hops.

In some embodiments, encapsulants may include tetrahydrocannabinol (THC)as a type of cannabinoids. THC may include delta-9-THC, delta-8-THC, andcombinations thereof. THC may comprise delta-6a,7-tetrahydrocannabinol,delta-7-tetrahydrocannabinol, delta-8-tetrahydrocannabinol,delta-9,11-tetrahydrocannabinol, delta-9-tetrahydrocannabinol,delta-10-tetrahydrocannabinol, delta-6a,10a-tetrahydrocannabinol, andcombinations thereof. Delta-9-tetrahydrocannabinol may comprisestereoisomers including (6aR,10aR)-delta-9-tetrahydrocannabinol,(6aS,10aR)-delta-9-tetrahydrocannabinol,(6aS,10aS)-delta-9-tetrahydrocannabinol,(6aR,10aS)-delta-9-tetrahydrocannabinol, and combinations thereof.

In some embodiments, one or more anti-bitterness agents are amongst theencapsulants. Examples of anti-bitterness agents include sodiumbenzoate, potassium sorbate, or inverted sugar. Certain anti-bitternessagents may also function as a preservative (e.g., sodium benzoate orpotassium sorbate) or a sweetener (e.g., an inverted sugar).

In some embodiments, encapsulants may include Alpha-pinene, Linalool,Myrcene, Limonene, Ocimene, Terpineol, Beta-caryophyllene, Geraniol,Alpha-humulene, Phellandrene, Carene, Terpinene, Fenchol, Borneol,Bisabolol, Phytol, Camphene, Sabinene, Camphor, Isoborneol, Menthol,Nerolidol, Guaiol, Isopulegol, Geranyl, Cymene, and Eucalyptol.

In some embodiments, a pH buffer may be used to maintain or adjust itspH. Examples of pH buffers include phosphoric acid and its salts orcitric acid and its salts (e.g., sodium or potassium salts).

In some embodiments, additives, such as natural or artificial flavoringagents, or natural or artificial coloring agents may be among theencapsulants. Examples of flavoring agents include flavor extracts (e.g.peach extract, orange extract, strawberry extract, oakwood extract).Examples of artificial coloring agents include FD&C, Blue No. 1, BlueNo. 2, Green No. 3, Red No. 40, Red No. 3, Yellow No. 5, and Yellow No.6. Examples of natural coloring agents include caramel E150, annattoE160b, chlorophyll E140, cochineal E120, betanin, turmeric E100, saffronE160a, paprika E160c, elderberry juice, pandan, and butterfly pea.

In some embodiments, it is preferred to use deionized (or distilled)water.

Various kinds of wines may be utilized, to be encapsulated or as themedium in which the particles are dispersed, including, but not limitedto, light wines, sparkling wines, fortified wines, vermouths, and otherfermented drinks. Other ethyl alcohols include, but are not limited to,distilled liquors such as whisky, rum, brandies (cognac, armagnac,applejack, kirsch, slivovitz, mirabelle, blackberry, peach), absinthe(made of brandy, wormwood, and other herbs), benedictine (made ofbrandy, sugar aromatic herbs), akavit, and vodka. Other ethyl alcoholsinclude, but not limited to, compounded liquors such as gin, cordial orliqueurs. In some embodiments, fruit cordials (e.g. apricots,blackberry, cherry, raspberry, and strawberry liqueurs), and plantcordials (e.g. crème de menthe, crème de cacao, and creme de rose,curacao, kummel, maraschino, and chartreuse) may be used.

In some embodiments, a plurality of antioxidants are used. Suchantioxidants may be selected from the group consisting of ethanol,polyethylene glycol 300, polyethylene glycol 400, propylene glycol,propylene carbonate, N-methyl-2-pyrrolidones, dimethylacetamide,dimethyl sulfoxide, hydroxypropyl-ß cyclodextrins,sulfobutylether-ß-cyclodextrin, a-cyclo dextrin, HSPC phospholipid, DSPGphospholipid, DMPC phospholipid, DMPG phospholipid, ascorbyl palmitate,butylated hydroxy anisole, butylatedhydroxy anisole, propyl gallate,a-tocopherol, y-tocopherol and any combination thereof.

In some embodiments, the first phase may further include a sweetener.Examples of suitable sweeteners include sugars, fructose, corn syrup,aspartyl peptide ester sweetener, sulfimide sweetener, ammoniatedglycyrrhizin, and inverted sugars. It is believed that in addition toimparting sweetness, sweetener additions may improve spherification asthe weight of that sweetener prevents a sphere from floating at thesurface of the second phase thereby negatively impacting mechanicalstrength or sphere integrity. Certain sweeteners may also function as athickening agent (e.g., fructose or an inverted Sugar).

In some embodiments, encapsulants may include flavors such as rose wine,mango rum, passionfruit rum, strawberry vodka, peach vodka, orangevodka, blueberry vodka, cantaloupe vodka, whiskey, coffee whiskey, hotjalapeno vodka, chocolate whiskey, PB&J vodka, chilli vodka, baconvodka, bubble gum vodka, whipped cream vodka, marshmallow vodka,strawberry shortcake vodka, fruitloops vodka, buttered popcorn vodka,cookie dough vodka, waffle vodka, glazed donut vodka, cookies and creamwhiskey, sesame and popcorn daiquiri, cinnamon churro vodka, pure milkvodka, quinoa vodka, smoked salmon vodka, sriracha vodka, pickle vodka,maple syrup vodka, rainbow sherbet vodka, root beer float vodka, cherryvodka, fireweed vodka, bison grass vodka, wasabi vodka, pineappleupside-down cake rum, asparagus gin, and saffron gin.

In some embodiments, the alcohol intended to be encapsulated may includewine, sherry, brandy, liqueurs, port, vodka, gin, whisky, scotch,cognac, tequila, rum, or champagne.

In some embodiments, encapsulants may include electrolytes, minerals,and vitamins. In some other embodiments, the encapsulated components aresimilar to hangover pills such as Dihydromyricetin (DHM), Prickly Pearextract, Milk Thistle, Spirulina, N-acetyl-cysteine, L-Theanine, Taurineplus vitamins, minerals.

In some embodiments, the encapsulated components consist of variousingredients. In some embodiments, a finished product may containdifferent type of particles with different release kinetics. Forexample, a beverage may contain two type of particles; particlescontaining alcohol and particles containing anti-hangover ingredients.The alcohol containing particles, in some embodiments, may have a fasterrelease kinetic. Then, the particles containing anti-hangoveringredients may have slower release kinetics to help the consumerexperience a better feeling after alcohol intake.

In some embodiments, a preservative may be among the encapsulants.Examples of preservatives include sodium benzoate, sodium metabisulfite,potassium sorbate, methylparabens, ethylparabens, propylparabens,butylpara bens, sorbic acid, acetic acid, propionic acid, sulfites,nitrites, sodium sorbate, calcium sorbate, benzoic acid, potassiumbenzonate, calcium benzonate, propylene glycol, benzaldehyde, butylatedhydroxytoluene, butylated hydroxyanisole, formaldehyde donors, essentialoils, monoglyceride, phenol, mercury components and any combinationthereof. It is believed that the preservative may effectively inhibitgrowth of bacteria, molds, or yeasts and extend shelf life of this firstcomposition without imparting any undesired changes in taste, odor,viscosity, or color thereto. Certain preservatives may also function asan anti-bitterness agent (e.g., sodium benzoate or potassium sorbate).

In some embodiments, the encapsulated ingredients may include ionicmultivalent components such as ionic zinc or ionic copper. Ionic zincmay refer to any compound or composition that may release zinc ion. Itmay be a zinc salt or a composition comprising a non-salt zinc compoundand a solubilizing agent that causes the non-salt zinc compound torelease zinc ions.

Organic zinc salts may include zinc acetate, zinc propionate, zincbutyrate, zinc formate, zinc gluconate, zinc glycerate(dihydroxypropionate), zinc glycolate (hydroxyacetate), zinc lactate,zinc pyruvate, and zinc gallate. Another class of organic zinc salts maybe made from di-carboxylic acids (which have two carboxy groups on asingle molecule), such as maleic acid, malonic acid, and succinic acid.The corresponding zinc salts are zinc maleate, zinc malonate, and zincsuccinate. Other organic salt candidates that are less soluble inaqueous solution and/or have relatively high pK values include zincsalicylate, zinc citrate, zinc oleate, zinc benzoate, zinc laurate, zincstearate, zinc valerate, and zinc tartrate. Inorganic salts, such aszinc chloride, zinc sulfate, and other similar salts, may also be used.

In some embodiments, the encapsulated ingredients may include a cationicpolymer such as polyamino acids (e.g. poly-(D, L or DL)-lysine salts,poly-(D, L or DL)-arginine salts, and all other forms of poly-cationicamino acid salts), polyamines (e.g. polymethylamine, polyethylamine,poly-n-propylamine, poly-iso-propylamine, polyethanolamine, polymethylethanolamine, polyethyl ethanolamine, ethyl diethanolamine, dimethylethanolamine, polymorpholine, poly-N-methylmorpholine,poly-N-ethylmorpholine, and mixtures thereof), poly((meth)acrylic acid)based copolymers with cationic groups (i.e. primary, secondary, tertiaryor quaternary amine) on the repeating monomer unit, cationic exchangeresins, proteins or peptides, and polysaccharides.

In some embodiments, the encapsulated ingredients may include a cationicsurfactant such as coconut alkyl amine acetate, stearyl amine acetate,lauryl trimethyl ammonium chloride, stearyl trimethyl ammonium chloride,cetyl trimethyl ammonium chloride, di-stearyl dimethyl ammoniumchloride, cetrimide, and alkylbenzyl dimethyl ammonium chloride (such asbenzalkonium or benzethonium type preservative, disinfectant andfungicide).

In some embodiments, the encapsulated ingredients may include athickener that may function to permit zinc to maintain its ionic state(e.g. glycerine, carrageenan, sugar, guar gum, and methylcellulose).

In the some embodiments, the release of the encapsulated ionic zinc maybe performed for an extended period of time (e.g. 5 min, 10 min, 30 min,60 min, 100 min, or 300 min) in the upper respiratory tract.

In some embodiments, the retention time of a droplet encapsulating ioniczinc may be prolonged by dispersing the droplets in a sticky hydrogelmedium such as xanthan gum or agar gum.

In some embodiments, an absorption enhancer or bioavailability enhancermay be among the encapsulants. An absorption enhancer or bioavailabilityenhancer selected from the group consisting of medium chain fatty acids,omega-3 fatty acids, capric acid, caprylic acid,(8-[2-hydroxybenzoyl]-amino)caprylic acid,N-(10-[2-hydroxybenzoyl]-amino)decanoic acid,N-(8-[2-hydroxybenzoyl]-amino)caprylic acid (SNAC, salcaprozate sodium),8-(N-2-hydroxy-5-chloro-benzoyl)-amino-caprylic acid (5-CNAC),N-(10-[2-hydroxybenzoyl]-amino)decanoic acid, alkylglycosides, chitosan,trimethylated chitosan, protease inhibitors, ß-glycoprotein inhibitors,dodecyl-2-N,N-dimethylamino propionate (DDAIP), zinc chelating agents(e.g. agar, ethylenediaminetetraacetic acid (EDTA), ethyleneglycol-bis(2-aminoethylether)-N,N,N,N′-tetraacetic acid (EGTA),1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA), andethylenediamine-N,N-diacetic-N,N′-di-β-propionic (EDPA)), calciumchelating agents (e.g. ethylene glycol tetraacetic acid, ethylenediamine tetraacetic acid (EDTA), salicylic acid, flavonoids (e.g.quercetin ((2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4Hchromen-4-one),luteolin), isoflavones (e.g. genistein(5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one)), flavonoid glycosides(naringin), alkaloids (e.g. sinomenine(7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one),triterpenoid saponins (glycyrrhizin[(3,18)-30-hydroxy-11,30-dioxoolean-12-en-3-yl2-O-glucopyranuronosyl-Dglucopyranosiduronic acid]), nitrile glycosides,phytomolecules (e.g. lysergol, allicin (garlic)), terpenes (ginkgolideA, B, C and J), ginsenosides, epigallocatechin, epigallocatechingallate, phenanthrene, cuminumcyminum Linn, herb, ginger, aloe vera,capsaicin, colchicine, vincristine, matrine, ammonium glycyrrhizinate,beeswax, piperine, trikatu, and their pharmaceutically acceptable salts(e.g. sodium), or derivatives (e.g. esters). In some cases, encapsulantsare suitable for being ingested by a human, or in some cases, theencapsulants are not suitable for human or animal ingestion, forinstance, active ingredients for topical creams or lotions.

5. Size

In some embodiments, particles are characterized by their size. Theparticle size distribution can be determined by sieve analysis. Unlessindicated otherwise, the particle size refers to the mean size.

In some embodiments, the particles are so small in diameter that theconsumer (e.g., a human) does not feel the particles as distinctentities in his/her mouth. In some other embodiments, the particles arebig enough in diameter that the consumer may bite down, squeezes orotherwise causes one or more such particles to break open in his/hermouth. In some other embodiments, the particles are big enough that theconsumer may feel them in his/her mouth but not too big that he/she maybite them. In some embodiments, different type of particles withdifferent encapsulated materials are mixed.

In some embodiments, the size of the particles is smaller than themouth-feel detection limit for human consumers, e.g., in a panel of 20consumers presented with a host material having a concentration ofbetween 5 and 50 particles per cubic centimeter, in a blind taste testwith comparing to a particle-free version of the host material, fewerthan 5 consumers will report that they may tell a difference inmouthfeel between the augmented and un-augmented version.

In some embodiments, the particles are larger, and the consumer maynotice a change in mouth-feel caused by the particles. In someembodiments, the mean size of the particles is less than 3 millimeters,less than 1 millimeter, less than 500 micrometers, less than 300micrometers, or less than 100 micrometers. The sizes may have adistribution, with a high-side characteristic size value, referred to asa maximum size. The maximum size is three standard deviations largerthan the mean size-ranges, and the same ranges as discussed above withrespect to mean sizes may apply to the maximum size. (Thus, a largeenough sample is likely to have some particles larger than the “maximumsize,” though they will be rare.) In some embodiments, the particlessizes within a sample are expected to exhibit a Gaussian distribution.

In some embodiments, the particles are less than 500, 100, 10, or 1micrometers in size. In some embodiments, the particles are less than500, 100, or 50 nanometers in size.

In some embodiments, the particles are less than 1, 0.2, 0.02, or 0.002cubic millimeters in volume. In some embodiments, the particles are lessthan 1, 0.2, or 0.2 cubic micrometers in volume. Volumes referenced aremean volumes unless indicated otherwise.

In some embodiments, the particles are filtered after manufacturing tonarrow the size distribution or remove the bigger particles. In someembodiments, filters may have a pore size of less than 1 millimeter, 500micrometers, 100 micrometers, 1 micrometer, 500 nanometers, or 100nanometers.

In some embodiments, the particles may be purified after manufacturingto remove the unreacted chemicals. In some embodiments, the particlesmay be purified using a variety of techniques. In some embodiments, theparticles were purified by spinning down the particles by centrifuge andwashing them multiple times with a solvent such as water. In someembodiments, the particles purified using other techniques such aspassing through a filter or sieve.

In some embodiment, the size and structure of the particles are tuned bychanging the type and concentration of the multivalent cations, theconcentration and molecular weight of the alginate, as well as the ratioand distribution of its guluronic (G) and mannuronic acid (M) units.Higher G/M ratio alginates may produce stiffer gels with bettermechanical integrity. The type and concentration of gelling ion (Ca²⁺,Sr²⁺, Ba²⁺), the presence of other ions such as sodium in the gellingsolution, and gelling time and temperature may also affect the size andstructure of the capsules. Divalent cations with higher affinities foralginate, such as Sr and Ba, are expected to cause formation ofinhomogeneous particles (dense shell, diffuse core), while the additionof non-gelling ions such as sodium to the gelling bath may increasehomogeneity.

In some embodiments, hydrophobicity of the oils may be tuned byintroducing a mixture of oils to produce micro- and nano-emulsions. Agoal of using such mixtures is to modulate the hydrophobicity to thepoint where a desired size or stability is reached for the disperseddroplets. In some embodiments, micro-emulsions have droplets with a mean(or median) diameter ranging from 1-1000 μm. In some embodiments, thedroplets have a mean (or median) diameter between 5-200 μm in size. Insome embodiments, the droplets have a mean (or median) diameter between10-25 μm in size. In some embodiments, nano-emulsions have droplets witha mean (or median) diameter ranging from 10-1000 nm in size. In someembodiments, the droplets have droplets with a mean (or median) diameterranging from 10-250 nm in size. In some embodiments, the droplets have amean (or median) diameter ranging from 15-25 nm in size.

In some embodiments, the size of the particles may be characterized bydynamic light scattering (DLS).

In some embodiments, the formed particles may undergo a purificationprocess to minimize or otherwise reduce the bitter taste of particlesencapsulating Cannabis extract (e.g. CBD and THC).

In some embodiments, particles may be passed through a hydrophilicfilter membrane with pore sizes ranging from 100-450 nm. This step isdone to remove (or reduce an amount of) particulate contaminationincluding micro-organisms, dust, metallic particles shed by theultrasonic horn, left-over plant matter, etc. The hydrophilic filteralso makes it likely that any unencapsulated, hydrophobic droplets havelow affinity for the membrane material.

In some embodiments, disposable syringe filters, including a plastichousing and a disc-shaped membrane, may be used to remove the mentionedimpurities. These disposable filters may be used for small-volume(10-30) sample filtration. Examples of appropriate hydrophobic materialsfor this purpose include nylon, polyethersulfone, cellulose acetate,regenerated cellulose, anopore, glass fiber, polypropylene, hydrophilicpolyvinylidene fluoride, and hydrophilic polytetrafluroethylene.

In some embodiments, disposable vacuum filtration systems, includingpolystyrene filter funnels, may be used to remove the mentionedimpurities. A vacuum pump may be connected to the assembly of thefilter, fitting, and the attached bottle to collect the sample. Thefilter funnel may be made of a hydrophilic membrane, with pore sizesranging from 100-450 nm, e.g., 220 nm. Disposable vacuum filtrationsystems may be utilized for purification of samples with volumes up to500 ml or larger.

In some embodiments, reusable in-line sterilizing filters, including ahydrophilic hollow fiber material packed into a plastic cartridge, maybe used to remove the mentioned impurities. These filters may have anetwork of long, hollow filaments with pore sizes ranging from 100-450nm, preferably 220 nm. The in-line sterilizing filters may be used forpurification of samples with volumes up to several liters at a time, orlarger. The sterilizing filters may be backflushed with water to clearout the particle matters that have stuck in the membrane, e.g., like inresponse to determining that more than a threshold amount of emulsionhas been filtered or exceeding a threshold pressure drop. Severalmethods, including small pumps, which are able to provide low flow rates(0.1-1 L/min), can be used to push the particles through the membrane.

In some embodiments, crossflow filtration may be used to continuouslypurify the particles.

6. Stability

In some embodiments, stabilizers have a hydrophobic tail with ahydrophilic head that facilitates placement of themselves in theinterphase of oil and water and stabilize the particles. In someembodiments, stabilizers may provide surface elasticity or stericstability for the particles in order to prevent or impede coalescence oraggregation over a wide pH range (e.g. pH of 2-7).

In some embodiments, the stabilizer may be chosen based on the size ofthe particles. For example, small molecule non-ionic surfactants, suchas polysorbates or sodium dodecyl sulfate (SDS), may be used tostabilize particles smaller than 200 nanometers while other surfactantssuch as lecithin or proteins may be used to stabilize particles biggerthan 200 nanometers.

In some embodiments, suspension stability may be measured usingzeta-potential analysis to determine the surface charge of the particlesin a surrounding medium. In some embodiments, suspension stability ismodified through various scenarios including addition of surfactants,viscosity modification of the continuous phase, change in particledensity, or change in particle size. In some embodiments, the net valueof the surface charge is kept above 10 mV to keep the particlesdispersed. In some other embodiments, the net value of the surfacecharge is kept above 5 mV to keep the particles dispersed. In some otherembodiments, the net value of the surface charge is kept above 15 mV tokeep the particles dispersed. In some other embodiments, the net valueof the surface charge is kept above 25 mV to keep the particlesdispersed. In some other embodiments, the net value of the surfacecharge is kept above 20 mV to keep the particles dispersed.

In some embodiments, dispersed-to-continuous (e.g. oil-to-water) phaseviscosity ratio is a factor for preparing stable emulsions. This ratiois defined by ε:

ξ=(ηd/ηc)

where ηd is the viscosity of the dispersed phase and ηc is the viscosityof the continuous phase. For a turbulent shear (e.g., with forms ofmixing implemented in the provisional application incorporated byreference above), a ε range of 0.5-5 is found to be optimal wheredroplet disruption is most efficient. In some embodiments, in order toreduce the ε value, low-viscosity oils (relative to that of thecontinuous phase) may be employed. In some embodiments, in order toreduce the ε value, the viscosity of the continuous phase may beincreased by the addition of thickeners or co-surfactants (e.g.,polyethylene glycol, or guar gum).

The volume fraction of dispersed phase (p) may be directly related tothe minimum diameter (dmin) of droplet. The increase in disperse phase(oil) volume fraction results in the increase in droplet size (atconstant process variables). Possible reasons could be the increase inemulsion viscosity, depletion of emulsifier and coalescence due to theincreased rate of collision frequency.

In some embodiments, a surfactant or a binary surfactant system may beused to facilitate the formation of stable oil droplets within thecontinuous aqueous phase. In emulsion systems, the reservoir of excessfree energy in the interfacial region generally is expected to result inan overall free energy that is well above the global minimum of thesystem. Such a colloidal system often cannot be formed by spontaneousdispersion; it is typically thermodynamically unstable, and any apparentstability may be regarded as a purely kinetic phenomenon. The emulsifiermay serve to reduce the interfacial tension between the two phases andreduce the amount of input required to overcome the surface energy.Emulsifiers additionally may stabilize the final dispersion bypreventing flocculation, coalescence, rupture, and separation into twoimmiscible phases. Therefore, the selection of appropriate surfactantsis helpful for emulsion formation and stability.

In colloidal food systems, which often include particles and droplets ofvarious kinds, particles may remain as individual units, but in manyinstances, aggregation takes place to form three-dimensional structures,referred as “gels.” The occurrence of aggregation phenomenon isdetermined by the general concept of the balance between attractiveforces (e.g. van der Waals) and repulsive forces. The latter may beelectrostatic from charged interfaces, steric from adsorbed polymers orfrom vesicles in the continuous phase, or a combination of forcesdepending on the composition of the food emulsion. In some O/W emulsionsdescribed herein, the adsorbed surfactants are the cause of repulsiveforces, prolonging the stability of particles. Ionic surfactants actmainly through electrostatic repulsion, while surfactants with apolymeric polar group provide steric repulsion as well as electrostaticeffects if the polar group is also charged.

Many surfactants used in food-grade emulsion are not water soluble. Thefirst class of such surfactants is those that are below the Krafft point(Krafft point: temperature at which the solubility of a surfactant isequal to its critical micelle concentration) at room temperature. Thesesurfactants not only form an adsorbed monolayer at the O/W interface butform additional phases to the two aqueous and oil liquids. The secondclass is the surfactants that have Krafft points well in excess of roomtemperature and exhibit temperature-dependent phase behavior. Evensurfactants with Krafft points below room temperature are classified aswater insoluble as a contrast to ionic surfactants, which formtransparent solutions at concentration levels of 30-40 wt %. On theother hand, for water-soluble surfactants, the adsorption of thesurfactant to the interface increases with the concentration in aqueoussolution until critical micelle concentration (CMC) is reached, at whichthe surfactant has formed a monolayer at the interface. Excesssurfactants in the system may form micelles.

The emulsifying capability of a surfactant can be classified accordingto the hydrophilic-lipophilic balance (HLB) of its molecules. HLB isdefined as the ratio of the weight percentage of hydrophilic groups tothe weight percentage of lipophilic groups in the molecule. The HLBscale has been created to classify non-ionic surfactants according totheir emulsifying properties. HLB values for commercially availablesurfactants range from 1 to 20. Surfactants with low HLB, ranging from 3to 6, promote the formation of W/O emulsions. Commonly used classes ofsuch emulsifiers are glycerol esters, propylene glycol fatty acidesters, polyglycerol esters, and sorbitol fatty acid esters. Surfactantswith HLB values ranging from 8 to 16 favor the formation of O/Wemulsions. This class of emulsifiers includes proteins, phospholipids,potassium and sodium salts, hydrocolloids, alginates, polyoxyethylenefatty acid esters, guar gum, etc.

Emulsifiers may be further categorized into low molecular masssurfactants (fatty alcohols, glycolipids, and fatty acids), and highmolecular mass surfactants extracted from naturally occurring materials,polysaccharides and proteins. Low molecular weight (LMW) surfactants aremobile at the interface and efficient in reducing the interfacialtension. Consequently, they coat the oil-water interface rapidly duringemulsification. Emulsifier concentration in the solution may play adecisive role to estimate the saturation radius of droplets resultingfrom emulsification, provided that, all other parameters are keptconstant. Besides concentration, physicochemical characteristics ofemulsifiers are also helpful for the formation and stability ofnanoemulsions. Low molecular weight nonionic emulsifiers (Tweens, Spans)facilitate preparing the droplets of very small size. However, it ischallenging to fabricate fine droplets from food biopolymers (proteins,modified starches, gums) due to their high molecular weight. Althoughprotein-based emulsifiers have an ability to produce smaller emulsiondroplets when used at lower concentrations than that of polysaccharides,high local intensities of ultrasonic treatment may denature the proteinas they are sensitive to higher temperatures.

In lecithin-based nano-emulsions, Ostwald ripening may be of minorimportance, especially in combination with highly non-polar oils.Physical stability may be obtained by employment of lecithin as anemulsifier, which is remarkably insoluble in water, and the choice of anoil with a distinctly low water solubility. Therefore, diffusion of theemulsified oil droplets through the aqueous medium is limited. However,it should be noted that an excess of lecithin decreases emulsionstability and results in the presence of vesicular lecithin aggregates.Thus, low amounts of surfactant are therefore considered not onlydesirable from a biological and cost efficiency viewpoint, but also fortechnological reasons. On the other hand, an increase in lecithinconcentration leads to the production of smaller particles due to anincreased surfactant to oil volume ratio, which in turn leads toenhanced physical stability. In contrast, large oil volume fractionslead to increased droplet collisions and hence coalescence duringemulsification. None of which is to suggest that embodiments are limitedto systems employing these techniques or any other described herein, asdiscussion of various design and engineering tradeoffs should not beread as implying any sort of disclaimer.

In some embodiments, using a single surfactant may lead to emulsionswith enhanced stability, possibly due to tighter molecular packing atthe oil/water interface.

In some embodiments, using a binary surfactant system may lead toemulsions with enhanced stability, possibly due to tighter molecularpacking at the oil/water interface. Use of binary surfactant systemallows for tuning of the HLB value. In some embodiments, the effectiveHLB value of the surfactants may be matched (or otherwise selected witha value that corresponds) with the HLB value of the carrier oil suitableto form O/W emulsions.

In some embodiments, the amount of surfactant(s) present in the systemmay range between 1 to 25% by volume. In some embodiments, the amount ofsurfactant(s) present in the system may range between 6 to 20% byvolume. In some embodiments, the amount of surfactant(s) present in thesystem may range between 8 to 14% by volume. Insufficient surfactantsmay lead to a higher energy input requirement to create O/W emulsions ofa certain size. Insufficient surfactants may lead to incomplete coverageof O/W emulsion, which may subsequently lead to droplet coalescence andphase separation. Excess surfactants may lead to formation of additionalmicelles. Excess surfactants may lead to an undesired increaseviscosity, affecting the energy required to form droplets.

In some embodiments, the stability of the resulting composition (e.g.,the emulsion, the result of adding an emulsion concentrate to a moredilute host food or beverage product, or one of these packaged fordistribution, like in a glass bottle, an aluminum can with a liner, apaper-based container with a liner, or a plastic bottle) may be measuredby various techniques such as particle size measurement, lightscattering, focused beam reflectance measurement, centrifugation,rheology and any combination thereof. Unless another measurement methodis specified, drop size measurement is used. Under this method,stability is indicated by monitoring the change in size of the particlesover time.

In some embodiments, the resulting composition is stable at roomtemperature for about 1 day to about 36 months. In some embodiments, thecomposition is stable at room temperature for about 1 months to 12months. In some embodiments, the composition is stable at roomtemperature for 3 to 6 months.

In some embodiments, presence of certain ingredients, such as flavoringagents or can liners, may change the stability of the solution byinteracting with certain active ingredients. For examples, full spectrumCBD may interact with aluminum can liners and physically adsorb to thewalls of the can and therefore reduce the available CBD in the solution.Some embodiments are expected to mitigate or eliminate this effect andimpart greater stability that is exhibited by traditional approaches byreducing these interactions with the exterior walls of resultingcapsules.

In some embodiments, the composition is stable at fridge temperature(e.g., less than 5° C.) for about 6 months to about 60 months. In someembodiments, the composition is stable at fridge temperature for about 1month to 12 months. In some embodiments, the composition is stable atfridge temperature for about 1 to 14 days.

In some embodiments, the composition is stable at about 40° C. for about2 months to about 12 months. In some embodiments, the composition isstable at about 40° C. for about 3 months to about 9 months. In someembodiments, the composition is stable at about 40° C. for about atleast one month. In some embodiments, the composition is stable at about40° C. for about at least one week. In some embodiments, the compositionis stable at about 40° C. for about at least one day.

In some embodiments, the composition's pH may range between 2 and 7.5.In some embodiments, the composition's pH may range between 2 and 4. Insome embodiments, the composition's pH may range between 4 and 7.

In some embodiments, a stabilizing agent may be present in thecontinuous aqueous phase. Once the droplets in an O/W Cannabis beverageemulsion have been formed during homogenization, it is helpful to keepthem stable throughout the expected lifetime of the product. Emulsionsmay become unstable through numerous physicochemical processes, whichare often highly dependent on the nature of the emulsifier used tostabilize the system. These physicochemical processes include theseparation of oil and water phases, coalescence, flocculation of oildroplets, and creaming of the droplets. In some embodiments, theemulsion comprises a stabilizer. In some embodiments, the stabilizer isalginate.

In some embodiments, salts or sugars are added to the interior waterphases to control the osmotic pressure gradients. In some embodiments,the concentration of the salt or sugar in the interior water phase is0.5 molar, 0.1 molar, 0.05 molar, or 0.01 molar. In some embodiments,the half-life of storage of the particles may be prolonged by balancingthe osmotic pressure between the interior and exterior water phases.

Failure to maintain an appropriate osmotic balance between inner andouter aqueous phases is a source of instability for W/O/W emulsionsduring storage (which is not to suggest that imbalanced systems or anyother subject matter are disclaimed). The osmotic pressure differencemay be zero or non-zero while still achieving good stability and highyield, but it should be low enough (in absolute value) to prevent orimpeded the coalescence or rupture of any swollen internal droplets. Acontemplated strategy is to attempt to reduce or eliminate the swelling(or shrinkage) of internal liquid droplets by converting them into softsolid-like particles through the gelation of biopolymer ingredients suchas starch or globular proteins.

7. Theory

In some embodiments, the terminal settling velocity (vs) of a particleis calculated using Stokes' law:

$\begin{matrix}{{{vs} = \frac{{g( {\rho_{p} - \rho_{w}} )}d_{p}^{2}}{18\mu}},} & (1)\end{matrix}$

wherein g is the gravitational acceleration constant (=9.81 m/s2), ρ_(p)is the particle's density (calculated based on the net density of acapsule based on its shell density and the density of the interiorphase), ρ_(w) is the medium's density, d_(p) is the particle's diameter(capsule outer diameter), and μ is the medium's viscosity. For example,a 500 μm capsule with a net density of 1600 kg/m3 would have a terminalsettling velocity of 0.08175 m/s in water (ρ_(w)=1000 kg/m3, μ=0.001N·s/m2). Next, the Reynold's number is calculated based on the vsobtained in the previous step. The aim here is to confirm whether theterminal velocity obtained adheres to Stokes' Law or a correction factormust be applied. Reynolds' number is given by:

$\begin{matrix}{{N_{R} = \frac{\varnothing v_{s}d_{p}\rho_{w}}{\mu}},} & (2)\end{matrix}$

where Ø is the shape factor of the particle (a perfect sphere would havea shape factor of unity). Following the example above, the calculatedReynold's number for a perfectly spherical particle would be 40.875. Thecalculated Reynold's number is significantly greater than the upperlimit for the Stokes' law calculation (1 is the upper limit); meaning acorrection factor (CD, drag coefficient) must be calculated and applied.The drag coefficient may be calculated by:

$\begin{matrix}{C_{D} = {\frac{24}{N_{R}} + \frac{3}{\sqrt{N_{R}}} + {{0.3}4}}} & (3)\end{matrix}$

Following the example above, CD would be ˜1.40. Now, the correctedterminal velocity is calculated by:

$\begin{matrix}{v_{s}^{2} = {\frac{4}{3}g\frac{( {\rho_{p} - \rho_{w}} )d_{p}}{C_{D}\rho_{w}}}} & (4)\end{matrix}$

Following the example above, the new vs is 0.053 m/s. Once again, theReynold's number calculation must be repeated and CD applied to theabove equation until the variation in vs reaches below 5%.To describe colloidal assembly and dissociation, the steric repulsionwill be described in conjunction with the DLVO potential (VDLVO) whichis a sum of the van der Waals (vdW) potential:

$\begin{matrix}{{V_{vdW} = {\frac{- A}{6}\lbrack {\frac{2a^{2}}{H( {{4a} + H} )} + \frac{2a^{2}}{( {{2a} + H} )^{2}} + {\ln ( \frac{H( {{4a} + H} )}{( {{2a} + H} )^{2}} )}} \rbrack}},} & (5)\end{matrix}$

where A is the Hamaker constant, H is the surface to surface separationdistance, and a is the particle radius and the electrostatic potentialVel which is given by:

$\begin{matrix}{{V_{el} = {\frac{64\; \pi \; {ak}_{b}T\; \Gamma_{0}^{2}n_{\infty}}{\kappa^{2}}{\exp \lbrack {{- \kappa}\; H} \rbrack}}},} & (6)\end{matrix}$

where n_(∞) is the bulk ion concentration, and κ⁻¹ is the Debye lengthgiven by:

$\begin{matrix}{{\kappa = {e\sqrt{\frac{z_{ion}n_{ion}}{ɛ_{r}ɛ_{0}k_{b}T}}}},} & (7)\end{matrix}$

where Z_(ion) is the valence and mon is the number density of ionsavailable in the solution, and εr is 78.4 for water. The parameter

$\begin{matrix}{\Gamma_{0} = \frac{{\exp \lbrack \frac{{ze}\; \psi_{0}}{2k_{b}T} \rbrack} - 1}{{\exp \lbrack \frac{{ze}\; \psi_{0}}{2k_{b}T} \rbrack} + 1}} & (8)\end{matrix}$

is a function of the valence z and the surface potential ψo.

In some embodiments, the particles are considered to be stable againstsedimentation or foaming when the terminal velocity of the particles ison the order of 10⁻⁸-10⁻⁷ m/s.

8. Mixing Techniques

In some embodiments, a high-shear rotor-stator device may be utilized tocreate coarse emulsions. A variety of stirrers, blenders andhomogenizers may be used for the purpose of creating emulsions.

In some embodiments, a high-energy acoustic ultrasonication device maybe utilized to create emulsions. Ultrasound-assisted emulsification isexpected to be suitable for creating nano-emulsions. Ultrasonicemulsification involves the exposure of immiscible phases to highintensity (e.g., high frequency or high amplitude suitable to causecavitation) acoustic waves, which is followed by the disruption ofdroplets (dispersed phase) under the influence of cavitation effects inthe liquid medium (continuous phase).

Acoustic emulsification is believed to be a two-step phenomenon. In thefirst step, dispersed phase droplets (or bubbles) are incorporated intothe continuous phase under the influence of Rayleigh-Taylor instability.Rayleigh-Taylor instability is the acceleration of one fluid into otherdue to acoustic waves at the media surface. In the second step, largerdroplets/bubbles are broken down into smaller ones due to cavitationprocess. The energy required by the continuous phase in the form ofshear to break or deform droplets of the dispersed phase may beexpressed in terms of the Laplace pressure (p):

$p = {{\gamma \lbrack {\frac{1}{R_{1}} + \frac{1}{R_{2}}} \rbrack} = \frac{\gamma}{2R}}$

In the above equation, R1 and R2 are the radius of curvature ofperfectly spherical droplets (thus, R1=R2), while γ is the interfacialtension of the droplets. When the applied shear stress is greater thanthe characteristic Laplace pressure, emulsions are created. Though,extremely high shear is often helpful in the case of nano-emulsions.

In dilute emulsions, where droplet coalescence is unlikely, dropletformation may be expressed in terms of the Weber number (We), which isthe ratio of the external disruptive energy (Ev) over surface energy(Es):

${We} = {\frac{E_{v}}{E_{s}} = \frac{{\rho_{c}( \overset{\_}{u} )}^{2}d_{\max}}{\gamma}}$

The equation above shows the Weber number for maximum stable dropletdiameter (dmax). Here, ρc is the continuous phase density, while ū isthe mean velocity difference across the droplet and γ is the interfacialtension of the droplets. volumetric acoustic energy density (Ev)expressed in W/cm3 or W/mL, is the energy (power) dissipated per unitvolume of sample for a given period of time:

$E_{v} = \frac{{energy}\mspace{14mu} {input}}{{dispersing}\mspace{14mu} {volume}}$

When the dispersed phase is added into the continuous phase, there is ahigh energy barrier to break planar interfaces and initiate theemulsification process. Disruption of droplets increases with increasingWeber number and it is expected that droplet break-up occurs when theWeber number is higher than a critical value. (a)² is a function ofaverage power dissipated per mass unit. Therefore, high-energydisruption forces are helpful to produce droplets of nanometer scale.

The resultant nano-emulsions are expected to show better stabilityagainst droplet aggregation than other emulsions, as their small dropletsize influences the Brownian motion and colloidal interactions (thoughembodiments are also consistent with other approaches that have lowerstability where other tradeoffs are made). The minimum size of a dropletduring emulsification (dmin) may be calculated depending on the type(Γsat) and concentration of emulsifiers (Cs) used:

$d_{\min} = \frac{6\; \Gamma_{sar}\phi}{C_{s}}$

Here, φ is the volume fraction of dispersed phase while Fsat (usuallyexpressed in mg/m2) is the surfactant load at saturation and defined asmass of emulsifier adsorbed per unit surface area of an interface whensurfactant concentration is in excess. Above equation, along with theturbulence phenomena, shows that droplets of small size may be formed byincreasing the concentration of emulsifiers, decreasing the volumefraction of dispersed phase, or using emulsifiers with a lowersurfactant load at saturation.

Additionally, immersion of the ultrasonic probe may be deep enough tostart cavitation. Otherwise, agitation will be the predominantphenomena, resulting in the production of potentially undesirableaerosols besides poor emulsification (again though, some embodiments mayimplement agitation without cavitation). Another issue is the erosion ofprobe tip, which can result in the contamination of emulsions with metalparticles. These particles may trigger oxidation and induce thedevelopment of off flavors in the prepared emulsions. Additionally,output energy of the probe with an eroded tip is decreased, therebyreducing the system efficiency.

In some embodiments, the total volume of the emulsions in a batch mayrange between 0.5 to 250 ml. In some embodiments, the total volume of aemulsion in a batch may range between 1 to 20 ml.

In some embodiments, the ultrasound sonication time ranges from 1 to 75minutes. The optimal processing conditions vary for differentformulations, since over-processing might lead to fluctuating dropletsizes. Over-processing is either caused by increased droplet collisionand re-coalescence rates upon increase of homogenization cycles orinsufficient emulsifier concentration in relation to the increasinginterfacial area. These two phenomena are often connected. If the newlycreated interfacial area is too large to be efficiently covered byemulsifying agents, the coalescence process is triggered. Thiscoalescence is often the limiting factor for droplet size reduction. Aplateau in particle size reduction with time is reached, where nofurther decrease of droplet diameters can be reached, or droplet sizeeven slightly increases. An aspect in this context is the influence ofthe temperature during production. Thermal energy is produced duringhigh-pressure homogenization. Efficient cooling may limit cavitationphenomena and prevent droplet re-coalescence. Moreover, the viscosity ofthe formulation can play a role. Increased inlet fluid viscosity couldpromote droplet rupturing through higher extensional stress and couldweaken re-coalescence phenomena.

In some embodiments, the ultrasound sonication time may range between 5to 25 minutes.

In some embodiments, the ultrasound sonication time may range between 1to 5 minutes.

In some embodiments, the ultrasound sonication time may range between 30seconds to 1 minute.

In some embodiments, a flow-through sonication system may be used toprepare the nano-emulsions in a continuous manner. In such embodiments,coarse micro-emulsions may be prepared in agitation tanks and fed to thesonication chamber via a pump. The micro-emulsions are subjected to highintensity ultrasonication and pumped back to the agitation tank.

In some embodiments, different droplet formation techniques (e.g. mixingtwo immiscible phases), such as microfluidization and ultrasonicationmay be applied in micro/nano encapsulation of different core (e.g.,encapsulated, not in the sense that they are “core” to the inventions)materials. In some embodiments, these techniques may be applied as asubsequent stage to the above operations, to break up larger dropletsformed with the techniques above. Some embodiments introduce energy intothe system (e.g., a mixture of larger droplets of the first phase in areservoir of the second phase) by subjecting the phases to vigorousmechanical agitation. The type of agitation which is expected to be mosteffective in this context is that which subjects the large droplets ofthe first phase to shear. Some embodiments may include an actuatorconfigured to apply such shear, e.g., by oscillating a plate immersed inthe mixture, by flowing the mixture through a tortuous path at high flowrates (e.g., with a Reynolds number of greater than 2100), by rotating ablade through the mixture, or the like. In this way, these droplets aredeformed from their stable spherical shapes and break up into smallerunits. In the presence of emulsifying agents, it is expected that astable emulsion of droplets will be formed.

One condition that is expected to influence emulsion formation istemperature. Interfacial tension and viscosity aretemperature-dependent, both decreasing with increase in temperature.Thus, raising the temperature of the liquids is expected to facilitateemulsion formation, subject to constraints from the heat sensitivity ofthe components.

In some embodiments, when viscosity of the first and second phases arelow (e.g., less than 3000 centipoises), turbine and propeller mixers maybe used to premix the phases prior to emulsification. In someembodiments, a stable emulsion may result from such mixing with nofurther treatment. In the case of higher viscosity liquids (e.g. morethan 2000 centipoises) and pastes, pan mixers, kneaders and some typesof continuous mixers may be used to disperse the first phase throughoutthe second phase. Tumbling mixers, such as those used for mixing powdersmay also be used for this purpose.

In some embodiments, droplets are formed (e.g., initially, or bysegmenting larger droplets) with a pressure homogenizer. In someembodiments, premixed phases (e.g., the above first phase and secondphase) are pumped through a narrow opening at high velocity (e.g. with aReynolds number of greater than 2100). The opening is provided between avalve and its seat. In some other embodiments, a pressure homogenizerincludes one or two valves and a high-pressure pump is used to form thedroplets. As the liquids pass through the gap, 15-300 um wide, betweenthe valve and seat, they are accelerated to speeds of 50-300 m·s⁻¹. Insome embodiments, the droplets of the internal phase (first phase) shearagainst each other, are distorted and break up into smaller units. Asthe liquids exit from the gap, there is a sudden drop in pressure. Somecavitation may occur. In some embodiments, a valve is designed to causethe droplets impinge on a hard surface (breaker ring) set at 90 degreesto the direction of flow of the liquids after they emerge from the gap.All these mechanisms are expected to stress the droplets and contributeto their disruption. Droplets diameters of 0.1-0.2 um is expected to beattainable in pressure homogenizers. It is expected that there is anapproximately inverse linear relationship between the logarithm of thehomogenizing pressure and the logarithm of the droplet diameter producedby a pressure homogenizer. Homogenizer valves may be made of stainlesssteel or alloys such as stellite. More erosion-resistant materials suchas tungsten carbide may be used, but tungsten carbide is not expected tobe suitable for some food applications (which is not to suggest thattungsten carbide or any other material is disclaimed). In someembodiments, the homogenizing valve may not have any passages other thanthe primary flow passage. The small droplets of the internal phase maycluster together. These may be dispersed by passing them through asecond valve. Some embodiments, thus, implement two-stagehomogenization. The first valve may be set at a higher gauge pressure,14-70 MPa, and the second valve may set be at a lower gauge pressure,2.5-7.0 MPa.

In some embodiments, a hydroshear homogenizer is used to form thedroplets (e.g. mixing two immiscible or partially miscible phases). Insome embodiments, the first and the second phases are pumped into acylindrical chamber at relatively low pressure, e.g., up to 2000 kPa.They may enter the chamber through a tangential port at its center andexit via two cone-shaped discharge nozzles at the ends of thecylindrical chamber. The liquids accelerate to a high velocity(sufficient to achieve Reynolds number greater than 2100) as they enterthe chamber, spread out to cover the full width of the chamber wall andflow towards the center, rotating in ever decreasing circles. High sheardevelops between the adjacent layers of liquid, destabilizing the largedroplets of the internal phase. In the center of the cylinder a zone oflow pressure is expected to develop and cavitation, ultrahigh frequencyvibration and shock waves are expected occur which all contribute to thebreak up of the droplets and the formation of an emulsion. Dropletssizes in the range 2-8 um is expected to be produced by this embodiment.

In some embodiments, a microfluidizer is used to form the droplets (e.g.mixing two immiscible phases). In some embodiments, separate streams ofthe first and the second phases may be pumped into a chamber under highpressure, e.g., 10 MPa. The liquids may be accelerated to high velocity,impinge on a hard surface and interact with each other. Intense shearand turbulence develop which is expected to cause breakup of thedroplets of the internal phase and the formation of an emulsion. Verysmall emulsion droplets are expected to be produced by recirculating theemulsion a number of times through the microfluidizer.

In some embodiments, a membrane homogenizer is used to form thedroplets. In some embodiments, the internal phase liquid is forced toflow through pores in a glass membrane into the external phase liquid,and an emulsion may be formed. Glass membranes may be manufactured withpores of different diameters to produce emulsions with different dropletsizes, e.g., in the range 0.5-10 um. Such membranes may produce o/w orw/o emulsions with very narrow droplet size distributions(polydispersity index of less than 1.2). In a batch version of thisequipment, the internal phase liquid may be forced (e.g., pumped)through a cylindrical membrane partly (e.g., between 10% and 90% along acentral axis)) immersed in the external phase (second phase) in avessel. In a continuous version, a cylindrical membrane through whichthe external phase flows may be located within a tube, through which theinternal phase flows. The internal phase may be put under pressureforcing it through the membrane wall into the external phase.

In some embodiments, an ultrasonic homogenizer is used to form thedroplets (e.g. mixing two immiscible phases). In some embodiments, aliquid is subjected to ultrasonic irradiation, causing alternate cyclesof compression and tension develop. This may cause cavitation in gasbubbles present in the liquid, resulting in the release of energy. Thisenergy may be used to disperse the first phase in the second phase andproduce an emulsion. In some embodiments, piezoelectric crystaloscillators may be immersed a reservoir. An ultrasonic transducer mayinclude a piezoelectric crystal encased in a metal tube. When ahigh-intensity electrical wave is applied to such a transducer, thecrystal oscillates and generates ultrasonic waves. In some embodiments,a transducer of this type is partly (e.g., more than 10%, 50%, or 90%)or entirely immersed in a vessel containing two liquid phases (e.g., thefirst phase and the second phase, as described above), together with anemulsifying agent or agents, and one phase may be dispersed in the otherto produce an emulsion. For the continuous production of emulsions on anindustrial-scale, mechanical ultrasonic generator may be used. A bladewith wedge-shaped edges may be clamped at one or more nodal points andpositioned in front of a nozzle through which the premixed emulsion ispumped. A resulting jet of liquid (the first and the second phases)emerging from the nozzle may impinge on the leading edge of the blade,causing the blade to vibrate at the blade's natural frequency, forexample, in the range 18-30 kHz. This is expected to generate ultrasonicwaves in the liquid, which is expected to cause one phase to becomedispersed in the other, which is expected to cause the formation of anemulsion. The pumping pressure may be relatively low, for example, inthe range 350-1500 kPa, and droplet diameters of the order of 1-2 um areexpected to be produced. In some embodiments, a modified ultrasonichomogenizer may be used to form the droplets where in another mixingtechnique is coupled with ultrasonic waves to provide better bulk mixingand keep the form droplets dispersed equally in the solution. In someother embodiments, the first and second phases may be mixed with anemulsifier machine (for example a turbo emulsifier) and then anultrasonic homogenizer may be used to further reduce the size of theformed droplets.

In some embodiments, a colloid mill may be used to form the droplets(e.g. mixing two immiscible or partially miscible phases). In someembodiments, the premixed emulsion ingredients pass through a narrowgap, in the range of hundreds of microns between a stationary surface(stator) and a rotating surface (rotor). In doing so, the liquid isexpected to be subjected to shear and turbulence, which is expected tobring about further disruption of the droplets of the internal phase anddisperses them throughout the external phase. The gap between the statorand rotor may be adjustable within the range 50-150 m. The rotor mayturn on a vertical axis in close proximity to the stator. The clearancebetween them may be altered by raising or lowering the stator by meansof an adjusting ring. Rotor speed ranges from 3000 rpm for a rotor 25 cmin diameter to 10 000 rpm for a smaller rotor 5 cm in diameter. Rotorsand stators may have smooth stainless steel surfaces. Carborundumsurfaces may be used when milling fibrous materials. Colloid mills maybe jacketed with heat exchangers for temperature control. This type ofmill is expected to be suitable for emulsifying viscous materials (e.g.2000 centipoises and more). For lower viscosity materials the rotor ismounted on a horizontal axis and turns at higher speeds, up to 15 000rpm. Mills fitted with rotors and stators with matching corrugatedsurfaces may also be used. The clearance between the surfaces maydecrease outwardly from the center. The product may be discharged underpressure, up to 700 kPa. Incorporation of air into the product isexpected to be limited and foaming problems are expected to be reducedin this type of mill relative to other approaches discussed herein.

In some embodiments, particles are generated using an electrostatic beadgenerator, with an electrostatic potential of 5-7 kV between a needle(with a hollow tube conveying liquid) feeding the first or second phaseand a gelling bath (e.g., in which a distal end of the needle isdisposed). In some embodiments, the first or second phase may be pumpedat a rate of ˜30 ml·h⁻¹ through the needle with an outer diameter of 0.4mm and a voltage of 7 kV, and the distance between the needle and thegelling bath may be 10 mm, which is expected to cause capsules with adiameter of 500 um to be generated. Smaller capsules with diameters downto 200 um are expected to be formed at lower flow rates, lower voltagesand smaller needles.

In some embodiments, a dripping method may be used to introduce dropletsof first phase to the second phase. Detachment of the droplet from thenozzle tip is fundamentally governed by Tate's Law. Droplets formed bythe dripping method are typically highly uniform in size and tend to belarge (e.g., larger than 1 mm, depending on the liquid) because of theaccumulation of drop volume at the nozzle tip before droplet breakup. Itis expected that the droplet size may be reduced by promoting dropletbreakup by applying external forces to an as-yet-unreleased droplet,such as air-driven shearing, forced vibration, electrostatic potential,and centrifugal force, actuators for which may be coupled to an orificeplate through which droplets are formed. Some embodiments may producemonodisperse capsules with sizes in the sub-millimeter range (e.g.,100-1000 um), and they are expected to achieve higher capsule productionrates when compared with the other dripping method. The dripping methodmay also be used to produce liquid-core capsules with either aqueous- oroil-phase cargo. To produce aqueous-core capsules, the cargo may bepre-mixed with divalent cations before its dropwise addition to a firstor second phase. Upon contact with the first or second phase, divalentcations at the droplet surface are expected to cross-link with thealginate polymer to form a continuous shell that encases the aqueouscore. Some embodiments form capsules with inverse gelation. In someembodiments, both the first or second phase and cargo (either aqueous oroil phase) may be pre-templated into compound droplets using aconcentric nozzle (with alginate as the outer flow and cargo as theinner flow). The compound droplets with cargo as the inner phase maythen be collected in a gelling bath to solidify the shell. Someembodiments form capsules with co-extrusion. The primary drawback ofusing the dripping method to form droplets or capsules is the lowproduction rate in terms of droplet number per unit time (which is notto suggest that this or any other subject matter is disclaimed). Theformation of droplets is on a drop-by-drop basis, and the maximumworking flow rate is often limited by the critical velocity before theextruded alginate liquid merges into a jet. One way to increase theprocess productivity to an industrial scale is by using multiplenozzles.

In some embodiments, particles are generated by atomization techniques.Some embodiments disperse the first phase into aerosolutions that may begelled to form microparticles. Various mechanisms by which the first orsecond phase may be atomized include the following: (i) pressure nozzle,(ii) co-axial nozzle, and (iii) rotary atomization. In some embodiments,the injecting solution may be extruded at a high velocity into quiescentair and fragmented into droplets by the drag force between the fluids.In some embodiments, the injecting solution is extruded by ahigh-velocity, co-flowing stream of air. The co-axial airflow exertsdrag on the first or second phase liquid surface, which thendisintegrates into tiny droplets. The breakup of the solution thread anddroplet is expected to occur when the dynamic pressure of the co-axialgas exceeds the pressure inside the liquid by a threshold amount. Insome embodiments, the first or second phase may be fed onto a disk orwheel that rotates at a high speed, e.g., greater than 100 rotations perminute (RPM), greater than 400 RPM, or greater than 600 RPM. Theresulting centrifugal force is expected to spread the first or secondphase onto the disk into a thin sheet (e.g. less than 100 micrometers,or less than 50 micrometers). The first or second phase eventuallydischarges at the peripheral edge of the disk as droplets that aresmaller than those existing before discharge. Some embodiments use spraynozzles that are employed in industry for spray drying. The mean size ofthe particles formed may be altered over a wide range, e.g., from 10 to100 um. In some embodiments, ultrasonic atomization may be used toproduce microparticles or microcapsules with mean sizes of 50-110 um.Generally, the size distribution of particles formed by the atomizationmethod is expected to be broad because of the chaotic disruption of theliquid thread or droplet under turbulent conditions. Nevertheless, thismethod is industrially attractive because of its high productivity andis there-fore useful in applications that do not require stringentcontrol over the size distribution.

In some embodiments, particles are generated by liquid-liquidtechniques. Some embodiments disperse a first or second phase in acontinuous phase of immiscible liquid (or partially miscible), which isexpected to form a template of water-in-oil (W/O) emulsion prior togelling. Some embodiments implement emulsification methods. The oilphase may be vegetable or mineral oil. Some embodiments may be used toproduce small alginate capsules, e.g., with a mean size diameter rangingfrom 1 to 1000 um. The factors influencing the droplet size profile inthe emulsification method are expected to include the alginateconcentration (or viscosity of the first or second phase), gellingconditions, and surfactant formulation. Channeled emulsification may beused to disperse the droplets. In some embodiments, the droplets may beformed one drop at a time from one channel, and the diameter of theresulting droplets may be limited by the length of the channel.Monodisperse droplets may be formed using uniform channel openings, suchas those used in microfluidics and membrane emulsification.Alternatively, or additionally, droplets may be dispersed bynon-channeled emulsification. Some embodiments cause the turbulentmixing of immiscible liquids through mechanical stirring by a rotor orstator or high-pressure homogenizers. The resulting droplets areexpected to have a broader size distribution than those formed viachannel emulsification because a liquid-liquid interface is createdthrough flow turbulence. Water in oil (W/O) emulsions are expected toform capsules immobilizing hydrophilic or large cargos, whereas oil inwater in oil (O/W/O) emulsion templates are expected to formmicrocapsules loaded with lipophilic cargos. Some embodiments implementan emulsification method referred to as the non-channeled method. Someembodiments use mechanical stirring, e.g., at stirring speeds below 1000RPM. The size of the capsules formed is expected to be inverselyproportional to the energy input during agitation. This method isexpected to produce capsules with a large range of mean size diameterbetween 20 and 1000 um, but the particle size distribution is expectedto be generally broad and polydisperse. In some embodiments, non-channelmethods, such as high-speed and high-pressure homogenization are used toproduce capsules with smaller mean sizes and size distributions that arenarrower and unimodal compared with those obtained by mechanicalstirring.

In some embodiments, particles are generated by using microfluidics.Several microchannel may be used to generate calibrated dropletsdepending on the type of technology used for the fabrication of themicrofluidic devices. For example, the inner diameter of a microchannelmay be 500, 100, 10, or 1 micrometer. With planar chips, designed usingsoft lithography or laser etching fabrication, examples ofconfigurations that may be used include the following twoimplementations. Periodic trains of monodisperse droplets may form bycolliding two immiscible fluids streams at a T-shaped junction, orperiodic trains of monodisperse droplets may form by using a flowfocusing microdevice (FFD), where a 2D planar co-axial stream is forcedto flow through a small orifice (e.g. diameter in the range of 200micrometers). With both configurations, experiments may be performedeither by imposing the flow rates or the pressure drop of the variousstreams. In each case, the mechanism of droplet formation which resultsfrom a subtle interplay between confinements, viscous and capillarystresses is expected to cause the production of periodic trains made ofmonodisperse droplets with extremely narrow size distribution. The meandroplet size is expected to be fine-tuned by adjusting the flowparameters of the various streams from 10 μm, typically the lateral sizeof the channels used, up to a few hundreds of microns. The mean dropletsize is expected to be decrease with the flow rate and viscosity of thecontinuous phase and increases with the flow rate of the dispersedphase. To decrease the droplet size, some embodiments may break thedrops into controlled daughter droplets at a T junction or at a junctionof various other angles. This passive method of break-up is expected tofacilitate modulating the size ratio of daughter droplets by modifyingthe hydrodynamic resistances of the two junction's outlets. It isexpected that this passive method of break-up may be carried out insuccession without increasing the polydispersity of the droplets untiltheir dimensions are larger than the channel dimensions. In someembodiments, monodisperse drops in larger sizes may be generated usingdouble capillary devices, by injecting the disperse phase through theco-flowing matrix fluid the setup includes a blunt calibrated needlewith a diameter φ of typically a few hundreds of micrometers, centeredto a cylindrical glass capillary with a diameter of D≥φ. Usingindependent syringe pumps, two immiscible fluids (the first and thesecond phases) may be respectively infused through both the needle andthe annular gap between it and the internal capillary wall. The flowrates may be independently controlled and adjusted in order to formmonodisperse droplets of the dispersed phase in the continuous one. BothW/O and O/W droplets may be prepared provided that the wettingproperties of the internal capillary wall are compatible with thecontinuous phase. Such devices then are expected to allow the extensionof the preparation of well calibrated emulsions up to sizes of a fewmillimeters. Emulsions with smaller sizes (typically a few tensmicrometers) are expected to be generated by using a double capillarydevice, which may include a cylindrical capillary tube co-axially nestedwithin a square glass.

In some embodiments, the size of the particles formed by liquid-liquidmethods is reduced by using a solvent diffusion method. The alginate maybe mixed with a solvent before dispersing the solution into droplets inan immiscible phase. Upon droplet formation, the solvent may be removed,thereby causing the alginate droplets to shrink. The addition ofdivalent cations causes the alginate droplets to gel.

In some other embodiments, a combination of techniques discussed aboveis used to form the droplets. Such combinations include using the mixingtechniques in parallel or one after each other. In some embodiments,different types of particles with different encapsulants are formed withdifferent ones of the above techniques and combined into a single hostmaterial.

9. Taste

In some embodiments, particles are expected to mask an unpleasant flavorof encapsulated components in order to keep the taste of the hostproduct pleasant, in some cases without affecting mouthfeel, and in somecases, while remaining shelf stable. For example, some consumers may notlike the taste of some type of alcohol while enjoying the effect ofalcohol consumption. Addition of alcohol-containing particles to fruitjuice or various other types of beverage is expected to provide theopportunity for the consumer to enjoy the effect of alcohol consumptionwithout experiencing the unpleasant flavor of alcohol.

In some embodiments, the effectiveness of masking a flavor of anencapsulated component is calculated by measuring the concentration ofthat component in the medium in which the particles are dispersed. Forexample, if whey protein is encapsulated, the concentration of the wheyprotein is monitored and measured in the medium in which the particlesare dispersed. As the whey protein is released from inside the particlesinto the medium, the concentration of the whey protein is changed in themedium and by monitoring this change, the effectiveness of the maskingthe flavor of the whey protein by particles and the release kinetics ofthe whey protein is calculated.

10. Permeability

In some embodiments, the particles contain an oil phase. In some suchcases, permeability of the particles is less of a concern compared toparticles containing water miscible components such as alcohol andproteins. Instead of permeability, stability of the particles is oftenmore important in case of oil-containing particles. In some such cases,the shell of the particles may be made of less polymers (such asalginate) and more stabilizers (such as surfactants). Stabilizers may beselected from the group of non-ionic, anionic, cationic or amphotericemulsifiers. The non-ionic emulsifiers used may be different emulsifiersfrom the group consisting of partial fatty acid esters, fatty alcohols,sterols, polyethylene glycols, such as ethoxylated fatty acids,ethoxylated fatty alcohols, and ethoxylated sorbitan esters, sugaremulsifiers, polyglycerol emulsifiers, and silicon emulsifiers. Theanionic emulsifiers used may be different emulsifiers from the groupconsisting of soaps, such as sodium stearate, fatty alcohol sulfates,mono, di- and tri-alkyl phosphoric acid esters and the ethoxylatesthereof, fatty acid lactate esters, fatty acid citrate esters, and fattyacid citroglycerin esters. Cationic emulsifiers may be, for example,quaternary ammonium compounds having a long-chain aliphatic group, suchas distearyldimonium chloride. Amphoteric emulsifiers may includedifferent emulsifiers from the groups consisting of alkylamininoalkanecarboxylic acids, betaines, sulfobetaines, or imidazoline derivatives.In some embodiments, naturally occurring emulsifiers are used such asbeeswax, lecithin, and sterol. In some embodiments, the final product isa stable oil in water emulsion.

In some embodiments, permeability of the particles may be tuned toprolong the shelf-life. In some embodiments, calcium chloride and zincsulphate are used to cross-link alginate microspheres prepared by anemulsification method. The particles cross-linked by a combination ofthese two salts are expected to show different morphology and slowerrelease compared with those cross-linked by the calcium salt alone. Zinccations may interact with the alginate molecules to a greater extentthan calcium cations. Zinc and calcium cations are expected to bind atdifferent sites of the alginate molecule The zinc cations may be lessselective and hence produce more extensive cross-linking of alginatewhich is expected to cause delayed release of the encapsulated firstphase.

Permeability of particles may be further tuned by addition of mono andpolysaccharides such as sucrose and chitosan. In some embodiments, thestability of particles is tuned by the amount of chitosan bound to theparticles. When the particles are made by dropping a solution of sodiumalginate into a chitosan solution (one-stage procedure), all thechitosan is located in a thin alginate/chitosan membrane on the surface.The permeability of these particles may be reduced by increasing thechitosan molecular weight and the degree of acetylation. The addition ofseveral layers of alginate and chitosan is expected to minimize thepermeation rates. In some embodiments, multilayers of alginate orchitosan are coated to control the permeation of the encapsulated firstphase.

In some embodiments, the permeation of particles may be controlled byvarying the ratio of guluronic acid (G-alginate) to mannuronic acid(M-alginate) content. While alginates with high guluronic acid contentdevelop stiff porous gels that maintain their integrity for long periodsof time, alginates rich in mannuronic acid residues are expected todevelop softer, less porous particles that tend to disintegrate faster.The affinity of alginates toward divalent ions may decrease in the orderPb>Cu>Cd>Ba>Sr>Ca>Co, Ni, Zn>Mn. Ca binds to G- and MG blocks, Ba to G-and M-blocks, and Sr to G-blocks solely. Different affinity is expectedto influence the physical properties of ionically crosslinked alginategels. High-G alginates are expected to be influenced by using ions ofhigh affinity (Ba or Sr), whereas for high-M alginates no effect isobserved on stability or permeability when using Ba or Sr in the gellingsolution

In some embodiments, the permeation of the particles is furthercontrolled by coating a layer or layers of polycations such aspolyethyleneimine, poly-L-ornithine (PLO), poly-D-lysine, poly-L-lysineand polymethylene-co-guanidine. In some other embodiments, use ofepimerized alginate or covalently cross-linked alginate may lead toreduced permeability of the particles. In some embodiments, use ofcations with higher affinity toward alginate may lead to reducedpermeability of the particles.

In some embodiments, permeation of the particles is further controlledby coating a layer or layers that are resistant to acidic breakdown aswell as pH differentials; such layers may protect the active ingredientsin the harsh conditions (e.g., surrounding medium before consumption oracidic environment of digestive tract) and release the activeingredients (e.g., encapsulants) in benign environment for probiotics,proteins, and peptides (e.g. in the colon that has a much lowerconcentration of proteolytic and other enzymes.) A much lowerconcentration of proteolytic and other enzymes are expected to bepopulated in the colon, as it is a much more benign environment forproteins and peptides as well as other biological entities such ascarbohydrates and nucleic acids.

11. Controlled Release

In some embodiments, the particles have a kind of “extended” or“delayed” release composition (relative to non-encapsulated versions ofactive ingredients), wherein the encapsulated materials are releasedover a prolonged period. Non-limiting examples include food andbeverage, oral care, personal care, and drug industries.

In some embodiments, the release rate of encapsulated components fromthe particles is determined by measuring the concentration ofencapsulated components in the solution in which the particles aredispersed.

In some embodiments, the particles comprise a pH sensitive componentsuch that known dissolution characteristics may be imparted to theencapsulant. Thus, for example, encapsulating compositions may beprepared according to methods known in the art such that upon exposureof the particles to a specific elevated or decreased pH, theencapsulating material rapidly dissolves, hardens, becomes permeable orthe like. In some embodiments, for example, the encapsulant is designedto dissolve in a solution of reduced pH. Thus, contact of the particlesof this embodiment with acidic environment of stomach is expected toresult in rapid dissolution of the particles, and release of thecontained alcohol composition into the stomach.

Release of an encapsulated component from a particle may be caused by avariety of mechanisms, including mechanical particle rupture, particlewall dissolution, particle wall melting or diffusion through the wall.In some embodiments, the difference in the concentration of theencapsulated component between inside and outside the shell of theparticle cause the mass transfer from the side with higher concentrationto the side with lower concentration. For example, if the particles areencapsulating vodka and are dispersed in water, the concentration of thealcohol molecules is higher inside the particles compared the outside.Therefore, the alcohol molecules will migrate through the pores of thepolymeric shell of the particles from inside toward outside theparticles because there is an effective osmotic pressure gradientbetween the interior and exterior of the particles. Same phenomenon willcause the water molecules to be transferred inside the particles.Therefore, the concentration of the alcohol and water will become equalin inside and outside of the particles eventually. Reducing the size ofthe pores of the polymeric shell or the concentration difference betweentwo sides of the polymeric shell is believed to prolong the releasekinetics. In addition, low molecular interaction of the encapsulatedcomponent with the outside medium is also believed to reduce the releaserate. For example, if oil is encapsulated inside the particles and theparticles are dispersed in water, the oil molecules have a very low andweak interaction with water molecules (low solubility) and therefore oilmolecules do not want to be transferred from inside the particles to thehydrophilic medium outside the particles.

In some embodiments, a solution may contain particles with differentrelease kinetics. In some embodiments, a solution containing particleswith different release kinetics may offer almost steady release of theencapsulated ingredients over a prolonged period of time. For example, asolution may contain particles, encapsulating protein, with differentrelease kinetics. Consumption of such a solution may lead to steadydelivery of protein to a consumer's body over a prolonged period oftime. In some embodiments, the prolonged period of time may be 1, 2, 5,10, or 20 hours. Delayed release may also be characterized relative tothe active ingredient in unencapsulated form, producing release curvesthat are delayed in their initial phases by 20% longer, 50% longer, 100%longer, 200% longer or more, and span after the start of release 20%longer, 50% longer, 100% longer, 200% longer or more than the span oftime over which release occurs in unencapsulated form.

In some embodiments, the release kinetics of active ingredients and theextent of absorption in humans or other in vivo may be studied byMass-balance pharmacokinetic studies, Absolute bioavailability studies,In vivo or in situ intestinal perfusion studies (e.g., in animals orhumans), In vitro permeation studies (e.g. in animals or humans), andother techniques known in the art.

In some embodiments, a particle may have a control release mechanism torelease an active ingredients immediately (e.g., after consumption by amammal, like a human), after some delay (e.g., 2, 4, 8, or 12 hoursafter consumption), an extended release (e.g. constant release over awindow of 0.5, 1, 2, 4, 6, or 12 hours), step-wise release (e.g. release50% of active ingredients in the first hour, no release in the secondhour, and release the other 50% of the active ingredients in the thirdhour after consumption), or a combination thereof. Such controlledrelease mechanism may be achieved through a single or multiple layers ina particle. In some cases, the same encapsulant may be encapsulatedmultiple different ways in different particles in a host alimentaryproduct, e.g., to produce a spike in release after a first amount oftime and then a different spike in release after a second amount oftime. Or different payloads may be encapsulated in different ways torelease at different times, e.g., releasing a stimulant after a firstamount of time and an anti-inflammatory agent later after a secondamount of time to aid in workouts and recovery. In some embodiments, anin-vitro dissolution rate of particles and the release profile of activeingredients was measured by USP apparatus type II or type III at variousconditions (e.g. at 37° C. and 50 rpm, in pH 6.8 buffer). Suchconditions were chosen to simulate the surrounding medium of particlesbefore consumption (e.g. in a beverage or an energy shot) and afterconsumption at different stages of digestive tract (e.g. colon or smallintestine). The term USP apparatus used herein is described e.g., in theUnited States Pharmacopeia XXV (2002).

12. Bioavailability

In some of the embodiments where lecithin is used as emulsifier for theproduction of O/W emulsions, the resultant nano-emulsions are highlyfluid and appear transparent or translucent. This transparency ortranslucency infers the presence of droplets smaller than 50 nmsuspended in the continuous aqueous phase. For applications wherebioavailability is of importance, the reduction in particle size provesto be beneficial; as the increased surface area to volume ratio of theparticles result in a higher interaction rate between the particle andits surroundings. Conversely, when the droplet diameter exceeds around100 nm, nano-emulsions appear hazy or white due to significant multiplescattering of light. The physical stability and shelf life ofnano-emulsions is superior to that of macroscopic emulsions. The dropletsize distribution is, for some use cases, one of the most importantphysical characteristics of nano-emulsions. In this disclosure, it isdetermined by dynamic light scattering (DLS). Furthermore, stability ofthe composition is measured using a technique selected from the groupconsisting of measuring drop size, light scattering, focused beamreflectance measurement, centrifugation, rheology and any combinationthereof.

In some embodiments, absorption enhancers may be used to promotemembrane permeability and improve oral bioavailability. SodiumN-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC) is an example of anabsorption enhancer.

13. Products

Some embodiments of the present application relate to food particlesobtained by the method described above. Some embodiments discloses amethod of producing a spherical alimentary-related particles thatcontains in its interior substances, characterized in that the diameterof the spherical food particle is in the range of 100 nm to 10 mm or, insome other embodiments, in the range of 1 micrometer to 1 mm or, in someother embodiments, 100 micrometers to 800 micrometers or, in some otherembodiments, 300 micrometers to 500 micrometers.

In some embodiments, the particles of the present disclosure may beprovided as a food composition in combination with a food carrier,including but not limited to food bars (e.g., granola bars, proteinbars, candy bars), cereal products (e.g., oatmeal, breakfast cereals,granola), bakery products (e.g., bread, donuts, crackers, bagels,pastries, cakes), dairy products (e.g., milk, yogurt, cheese), beverages(e.g., milk-based beverages, sports drinks, fruit juices, teas, softdrinks, alcoholic beverages, bottled waters), beverage mixes, pastas,grains (e.g., rice, corn, oats, rye, wheat, flour), egg products, snacks(e.g., candy, chips, gum, gummies, lozenges, mints, chocolate), meats,fruits, vegetables or combinations thereof. Food compositions maycomprise solid foods. Food compositions may comprise semi-solid foods.Food compositions may comprise liquid foods. A composition in a liquidform may be formulated from a dry mix, such as a dry beverage mix or apowder. A dry mix may be suitable in terms of transportation, storage,or shelf life. The composition may be formulated from the dry mix in anysuitable manner, such as by adding a suitable liquid (e.g., water, milk,fruit juice, tea, or alcohol).

In some embodiments, the particles of the present disclosure maycomprise pet or other animal products, such as animal food (e.g., dogfood, cat food), treats, and nutritional supplements (e.g., liquids,sprays, or powders for application to food or water). These compositionsmay be formulated for or administered to domestic or pet animals (e.g.,dogs, cats, small mammals, birds), livestock and other farm animals(e.g., cows, pigs, horses, sheep, goats), zoo animals, or any othervertebrates. Compositions for administration to animals may beformulated with microencapsulated cannabinoid-rich oil ornon-encapsulated cannabinoid-rich oil, alone or in combination withessential oils, terpenes, and other components described herein.Compositions for administration to animals may be mixed into feed orwater, prepared for spraying application (e.g., mixed in glycerin), forintravenous administration (e.g., in a syringe or an IV bag), in salves,vitamins, liquid vitamin pumps, treats, or other forms.

In some embodiments, the particles are intended as food productadditives, including during fruit preparation, in yogurts, or as an icecream topping. In some embodiments, the particles may be served atvarying temperatures: from frozen, to slightly chilled, to roomtemperature, warm and even quite hot. In some embodiments, other typesof polysaccharides are used instead of sodium alginate such asagar/agarose, k-carrageenan, pectin, gellan gum, and chitin.

In some embodiments, the particles will have an expected shelf life ofabout 1 year. In some other embodiments, the particles will have anexpected shelf life of about 6 months. In some other embodiments, theparticles will have an expected shelf life of about 2 months. In someother embodiments, the particles will have an expected shelf life ofabout 1 month. In some other embodiments, the particles will have anexpected shelf life of about 1 week. In some other embodiments, theparticles will have an expected shelf life of about 1 day. Suchparticles should tolerate a wide range of temperatures without affectingquality. The permeability of the particles is another factor indetermining the shelf life of the particles. In some embodiments, theparticles are stable in the temperature range of 0-40 degrees ofCelsius. In some other embodiments, the particles are stable in thetemperature range of 15-30 degrees of Celsius.

In some embodiments, the particles may be dispersed in a lubricant.Particles may contain various types of encapsulants, including essentialoils and analgesics.

In some embodiments, the particles may be dispersed in a sanitizer.Particles may contain various types of encapsulants, including essentialoils and antibacterial ingredients.

14. Characterization and Uses

In some embodiments, shelf-life of the products is predicted using thedata collected during accelerated testing to produce a model forprediction. The data, in some embodiments, is matched with commonreaction kinetic formulas or extrapolated to predict capsule performanceover future time points and the shelf-life of the product. In someembodiments, sufficient number of experiments are performed to test thedifferent storage stability variables, such as temperature, time andhumidity. In some embodiments, 50 experiments at different conditionswere performed. In some embodiments, 100 experiments at differentconditions are performed. In some embodiments, more 100 experiments atthe same conditions are performed. In some embodiments, for flavors,orange oil is used an example of an encapsulant. Orange oil is a flavorcomponent that may be encapsulated to control release and preventoxidation. In some embodiments, to compare the performance of orange oilencapsulated particles, samples are analyzed for limonene and limoneneoxide formation over the course of 70 days at 37° C.

In some embodiments, in situ particle performance is analyzed using anoxygen sensitive fluorescent dye to monitor the oxygen exposure ofencapsulants. In some embodiments, the stability and prediction ofshelf-life of particles is dependent upon the particle formulation,system metrics, and final application.

In some embodiments, the dispersed phase of a product (e.g., a beverageor an energy shot) includes one or more particles. The particles arestable and do not dissolve in the dispersion medium. In someembodiments, when the dispersion medium has a certain viscosity, theparticles may stay uniformly dispersed throughout the dispersion medium.In some embodiments, the particles may be settled at the bottom of adispersion medium or be floating at the top of the dispersion medium andthen dispersed by shaking the dispersion medium.

In some embodiments, a dispersion medium may include pH modifiers formodifying the pH of the dispersion medium. The pH of the dispersionmedium may need to be adjusted with the pH modifier in order to providea medium that will not degrade the particles dispersed therein at a fastrate to provide the desired shelf life stability.

In some embodiments, the formed particles may be encapsulated again inbigger particles. In some embodiments, the reason behind such processmay be increasing the shelf life. In some other embodiments, the reasonbehind such process may be achieving different release timelines fordifferent components where the encapsulated materials inside smallerparticles would be released later than the encapsulated materials insidethe bigger particles. In some embodiments, there is one particle insidethe bigger particles. In some other embodiments, there are multiplesmall particles inside one big particle. In some embodiments, it may bea combination of the previous two.

In some embodiments, the term “adding” refers to joining two or morethings together. In some embodiments, adding comprises joining twoingredients together.

Herein, the term “dissolving” refers to converting the particle of acompound to a lower state of stability and volume. In some embodiments,dissolving comprises forming a solution by placing a solid into aliquid. In some embodiments, dissolving comprises forming a homogenousmixture of a liquid and oil. In some embodiments, dissolving comprisesforming a homogenous aqueous mixture.

Herein, the term “solution” refers to a mixture or formulation of two ormore compounds. In some embodiments, the solution is a mixture of two ormore liquids.

Herein, the term “spraying” refers to dispersing a compound or compoundsinto fine particles or droplets. In some embodiments, spraying includesdispersing a liquid into a fine mist.

Herein, the term “evaporating” refers to converting a compound into thevapor phase. In some embodiments, evaporating includes heating acompound. In some embodiments, evaporating comprises changing pressure.In some embodiments, evaporating includes turning a liquid into a gas.

Herein, the term “combining” refers to merging, incorporating, fusing,blending, or mixing. In some embodiments, combining comprises mixingcompounds to form a homogeneous mixture.

In some embodiments, the encapsulation process is performed at ambienttemperature. An increase or decrease in temperature, as well asincreasing the production costs of the particles, may affect theviscosity, density and surface tension of the oily and aqueous phasespresent in the process. In some cases, the process may be tuned toaccommodate other temperatures.

The term “about,” “nearly,” “substantially,” and the like, as usedherein refers to within +/−20% of the designated amount, unlessindicated otherwise, which is not to suggest that terms lacking thesequalifiers are to be read as limited to the exact recited value ifindustry practice is to allow for some tolerance around the recitedvalue (e.g., if one of ordinary skill in the art would understandreference to 10% alcohol concentration in a host beverage to encompassanything in the range of 8% to 12% under industry practice and typicalvariation in a manufacturing process around a target value).

In some embodiments, the particles are separated from one another by ahost beverage, e.g., less than 20%, less than 10%, less than 1%, or lessthan 0.01% of the particles are in contact under the above solubilitytest.

It will be appreciated that preferred properties of a particle (e.g.,size, material, structure, and etc.) may be readily determined by thoseskilled in the art by evaluating the application and product. It is thecombination of materials, method and form of application that producethe desired particle, which one can determine only from experiments.

FIG. 12 depicts a method 1200 of operation, in accordance with someembodiment, and may generally include adding some particles, inaccordance with some embodiments of the present disclosure, to adispersion medium in a container, as an alimentary product, to achievesome of the following steps: isolating encapsulants from the dispersionmedium in the alimentary product as shown in block 20, concealing (e.g.,fully or partially) the flavor of encapsulants (or at least some ofthem) while the alimentary product is ingested without affectingmouthfeel of the alimentary product as shown in block 22, delaying (orcontrolling) the release of the encapsulants (or at least a portion ofthe encapsulants) in the digestive tract as shown in block 24, releasingthe encapsulants in the digestive tract as shown in block 26, andenhancing the bioavailability of the encapsulants as shown in block 28.

FIG. 13 illustrates a container (e.g., a can or a bottle) 1301containing a host medium (e.g. a beverage) 1302 and particles 1303,containing an encapsulant, dispersed in the host medium. The container1300 may have an opening. In some embodiments, the particles may beuniformly dispersed throughout the host medium. In some embodiments, theparticles may be settled (e.g. fully or partially) at the bottom of thecontainer. In some embodiments, the particles may be floating (e.g.,fully or partially) on the top of the host medium. in some embodiments,some of the particles may be in surface contact with each other. In someembodiments, particles are isolated from each other by the host medium.

In some embodiments, the particles similar to the particle shown in FIG.4 are used in immune booster products. Such products may be packaged in2 oz. (or 1 oz.) format to deliver 20 mg ionic zinc, 1000 mg vitamin C,600 IU and vitamin D3. In some embodiments, the 2 oz. format contain 20mg CBD as well. Containers may be less than or equal to 50 gallons, 5gallons, 1 gallon, 1 quart, 12 oz, 5 oz, or 2 oz.

In some embodiments, the particles may contain encapsulants withantimicrobial activities. In some embodiments, the particles may containencapsulants with antirhinoviral activity (e.g. ionic zinc).

In some embodiments, particles, containing encapsulants withantirhinoviral activity, may be used in an immune booster product toenhance the taste (e.g. by masking the flavor of bad tasting ingredientssuch as ionic zinc), keep the encapsulants in the right format (e.g.keep the zinc in ionic format by a complexing agent such as agar), orprovide controlled released at various stages of digestive tract (e.g.oropharyngeal region).

In some embodiments, particles, containing encapsulants withantirhinoviral activity, may be used as in dental-related products suchas mouthwash.

In some embodiments, particles may be dispersed in a hydrogel medium,with sticky texture (e.g. xanthan gum), to provide a coating inoropharyngeal region. The particles may contain encapsulants to bereleased in the oropharyngeal region. The release may be controlled totake place over an extended period of time (e.g. 1, 5, 10, 30, 90, 150minutes).

In some embodiments, the surface of particles may be coated with variouscoatings to better meet the requirements of an intended application. Forexample, the surface of the particles may be coated with a sticky layer.Such sticky particles may be used to deliver encapsulants to theoropharyngeal region with controlled release kinetics. For example, suchparticles may contain ionic zinc as an encapsulant to be released in theoropharyngeal region to inhibit the normal cleavages of viralpolypeptides (e.g. SARS-CoV-2).

In some embodiments, particles may be added to a cream or a lotion toprovide controlled release of encapsulants (e.g. essential oils or CBD).For example, the particles may be added to a skin care formulation,where the particles may seal moisture into the skin to prevent dryingand re-hydrate dried skin.

In some embodiments, particles may be added to a hand sanitizer toprovide an extended release of an encapsulant with antimicrobialactivities (e.g. essential oils or ethyl alcohol).

In some embodiments, particles may be used to provide controlled releaseand targeted delivery of pharmaceuticals in the conserved regions ofinfluenza for effective antiviral activity.

In some embodiments, particles may be used in an antimicrobial emulsion.Such antimicrobial composition may include essential oils stabilized ina hydrogel medium.

It will be appreciated that any encapsulating, non-toxic material may beused according in some embodiments to deliver the ethanol compositionfor recreational purposes. However, it is preferred for theencapsulating material to be digestible, in instances where theencapsulating material is designed to be ingested along with thecontents. In such instances, the encapsulating material should becomprised of gelatin or alginate or like digestible material, and theparticles may be designed for breakage in the consumer stomach and upperintestine. To that end, it may be, in addition, desirable for theparticles to be coated with a sugar coating or the like, such that asthe particles contacts the salivary juices in the mouth, additionalsaliva is produced, the particles have a pleasant taste, and as thesugar dissolves, it ensures ease of swallowing the broken or unbrokenparticles.

It will be appreciated from this disclosure that it is preferred for theencapsulating material to be capable of sustaining variousconcentrations of ethanol within the internal compartment, withoutdissolution into the ethanol. It is also preferred for the encapsulatingmaterial to be of sufficient rigidity to sustain packaging and storagefor from several minutes to several weeks or months. This goal isachievable using gelatin, if sufficient concentrations of gelatin areincorporated into the encapsulating material, or where the moleculesconstituting the gelatin particles are cross-linked with a cross-linkingagent, such as but not limited to glutaraldehyde. Methods of achievingthis goal are known in the art and therefore, are not discussed indetail here. Alternative encapsulating materials which meet thesecriteria include waxes, synthetics and the like, which are non-toxic andstable in the presence of ethanol compositions.

Having generally described some embodiments of this application, thefollowing examples are provided to provide detailed written disclosureof some of the embodiments of this application. However, the scope ofthis application should not be construed as being limited by thespecifics of these examples. Rather, the scope of this applicationshould be determined through reference to the complete disclosure andthe claims appended hereto. It should further be noted that while thefollowing examples provide descriptions of specific compositions ofmatter, produced according to disclosed small-scale processes, thoseskilled in the art will appreciated that highly automated andmechanized, large-scale methods for producing the encapsulated productsof this application come within the scope of this application.

The reader should appreciate that the present application describesseveral independently useful techniques. Rather than separating thosetechniques into multiple patent applications, applicants have groupedthese techniques into a single document because their related subjectmatter lends itself to economies in the application process. But thedistinct advantages and aspects of such techniques should not beconflated. In some cases, embodiments address all of the deficienciesnoted herein, but it should be understood that the techniques areindependently useful, and some embodiments address a subset of suchproblems or offer other, unmentioned benefits that will be apparent tothose of skill in the art reviewing the present disclosure. Due to costsconstraints, some techniques disclosed herein may not be presentlyclaimed and may be claimed in later filings, such as continuationapplications or by amending the present claims. Similarly, due to spaceconstraints, neither the Abstract nor the Summary of the Inventionsections of the present document should be taken as containing acomprehensive listing of all such techniques or all aspects of suchtechniques.

It should be understood that the description and the drawings are notintended to limit the present techniques to the particular formdisclosed, but to the contrary, the intention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the present techniques as defined by the appended claims.Further modifications and alternative embodiments of various aspects ofthe techniques will be apparent to those skilled in the art in view ofthis description. Accordingly, this description and the drawings are tobe construed as illustrative and are for the purpose of teaching thoseskilled in the art the general manner of carrying out the presenttechniques. It is to be understood that the forms of the presenttechniques shown and described herein are to be taken as examples ofembodiments. Elements and materials may be substituted for thoseillustrated and described herein, parts and processes may be reversed oromitted, and certain features of the present techniques may be utilizedindependently, all as would be apparent to one skilled in the art afterhaving the benefit of this description of the present techniques.Changes may be made in the elements described herein without departingfrom the spirit and scope of the present techniques as described in thefollowing claims. Headings used herein are for organizational purposesand are not meant to be used to limit the scope of the description.

As used throughout this application, the word “may” is used in apermissive sense (i.e., meaning having the potential to), rather thanthe mandatory sense (i.e., meaning must). The words “include”,“including”, and “includes” and the like mean including, but not limitedto. As used throughout this application, the singular forms “a,” “an,”and “the” include plural referents unless the content explicitlyindicates otherwise. Thus, for example, reference to “an element” or “aelement” includes a combination of two or more elements, notwithstandinguse of other terms and phrases for one or more elements, such as “one ormore.” The term “or” is, unless indicated otherwise, non-exclusive,i.e., encompassing both “and” and “or.” Terms describing conditionalrelationships, e.g., “in response to X, Y,” “upon X, Y,”, “if X, Y,”“when X, Y,” and the like, encompass causal relationships in which theantecedent is a necessary causal condition, the antecedent is asufficient causal condition, or the antecedent is a contributory causalcondition of the consequent, e.g., “state X occurs upon condition Yobtaining” is generic to “X occurs solutionely upon Y” and “X occursupon Y and Z.” Such conditional relationships are not limited toconsequences that instantly follow the antecedent obtaining, as someconsequences may be delayed, and in conditional statements, antecedentsare connected to their consequents, e.g., the antecedent is relevant tothe likelihood of the consequent occurring. Statements in which aplurality of attributes or functions are mapped to a plurality ofobjects (e.g., one or more processors performing steps A, B, C, and D)encompasses both all such attributes or functions being mapped to allsuch objects and subsets of the attributes or functions being mapped tosubsets of the attributes or functions (e.g., both all processors eachperforming steps A-D, and a case in which processor 1 performs step A,processor 2 performs step B and part of step C, and processor 3 performspart of step C and step D), unless otherwise indicated. Further, unlessotherwise indicated, statements that one value or action is “based on”another condition or value encompass both instances in which thecondition or value is the solution factor and instances in which thecondition or value is one factor among a plurality of factors. Unlessotherwise indicated, statements that “each” instance of some collectionhave some property should not be read to exclude cases where someotherwise identical or similar members of a larger collection do nothave the property, i.e., each does not necessarily mean each and every.Limitations as to sequence of recited steps should not be read into theclaims unless explicitly specified, e.g., with explicit language like“after performing X, performing Y,” in contrast to statements that mightbe improperly argued to imply sequence limitations, like “performing Xon items, performing Y on the X'ed items,” used for purposes of makingclaims more readable rather than specifying sequence. Statementsreferring to “at least Z of A, B, and C,” and the like (e.g., “at leastZ of A, B, or C”), refer to at least Z of the listed categories (A, B,and C) and do not require at least Z units in each category. Unlessspecifically stated otherwise, as apparent from the discussion, it isappreciated that throughout this specification discussions utilizingterms such as “processing,” “computing,” “calculating,” “determining” orthe like refer to actions or processes of a specific apparatus, such asa special purpose computer or a similar special purpose electronicprocessing/computing device. Features described with reference togeometric constructs, like “parallel,” “perpendicular/orthogonal,”“square”, “cylindrical,” and the like, should be construed asencompassing items that substantially embody the properties of thegeometric construct, e.g., reference to “parallel” surfaces encompassessubstantially parallel surfaces. The permitted range of deviation fromPlatonic ideals of these geometric constructs is to be determined withreference to ranges in the specification, and where such ranges are notstated, with reference to industry norms in the field of use, and wheresuch ranges are not defined, with reference to industry norms in thefield of manufacturing of the designated feature, and where such rangesare not defined, features substantially embodying a geometric constructshould be construed to include those features within 15% of the definingattributes of that geometric construct. The terms “first”, “second”,“third,” “given” and so on, if used in the claims, are used todistinguish or otherwise identify, and not to show a sequential ornumerical limitation. As is the case in ordinary usage in the field,data structures and formats described with reference to uses salient toa human need not be presented in a human-intelligible format toconstitute the described data structure or format, e.g., text need notbe rendered or even encoded in Unicode or ASCII to constitute text;images, maps, and data-visualizations need not be displayed or decodedto constitute images, maps, and data-visualizations, respectively;speech, music, and other audio need not be emitted through a speaker ordecoded to constitute speech, music, or other audio, respectively.

The present techniques will be better understood with reference to thefollowing groups A-G, each including enumerated embodiments:

Group A:

-   1. A method of encapsulation, the method including: providing a    first mixture, the first mixture including: a first plurality of    lipophilic carriers; a first plurality of active ingredients; a    first polymer; and a first plurality of emulsifying agents; applying    heat to the first mixture until the first mixture reaches a first    temperature; providing a second mixture, the second mixture    including: an aqueous solution; and a second polymer; applying heat    to the second mixture until the second mixture reaches a second    temperature; mixing the first mixture with the second mixture to    obtain a third mixture; providing a fourth mixture, the fourth    mixture including: a second plurality of lipophilic carriers; a    third polymer; and a second plurality of emulsifying agents;    applying heat to the fourth mixture until the fourth mixture reaches    a third temperature; mixing the third mixture with the fourth    mixture to obtain a fifth mixture; providing a sixth mixture, the    sixth mixture including: an aqueous solution; applying heat to the    sixth mixture until the sixth mixture reaches a fourth temperature;    and mixing the fifth mixture with the sixth mixture to obtain a    seventh mixture.-   2. The method of embodiment 1, wherein: the first polymer has a    first glass transition temperature; and the first temperature is    above the first glass transition temperature.-   3. The method of embodiment any one of embodiments 1-2, wherein: the    second mixture has a third plurality of emulsifying agents.-   4. The method of any one of embodiments 1-3, wherein: the fourth    mixture further including: a crosslinking agent for the second    polymer.-   5. The method of any one of embodiments 1-4, wherein: the first    polymer has a first glass transition temperature; the third polymer    has a second glass transition temperature; and the first glass    transition temperature is higher than the second glass transition    temperature.-   6. The method of any one of embodiments 1-5 further including:    adding a thickening agent to the seventh mixture, wherein the    thickening agent is a polysaccharide.-   7. The method of any one of embodiments 1-6, wherein: the first    plurality of emulsifying agents is selected from the group    consisting of an extract of Quillaja, lecithin, monoglycerides,    polysorbate 80, polysorbate 20, Polyglycerol polyricinoleate, gum    Acacia, Xanthan gum, sorbitol, mannitol, glycerol, and sodium    alginate.-   8. The method of any one of embodiments 1-7, wherein: the first    plurality of emulsifying agents has a first hydrophilic-lipophilic    balance value; the second plurality of emulsifying agents has a    second hydrophilic-lipophilic balance value; and the first    hydrophilic-lipophilic balance value is higher than the second    hydrophilic-lipophilic balance value.-   9. The method of any one of embodiments 1-8, wherein: the sixth    mixture further including: a third plurality of emulsifying agents.-   10. The method of any one of embodiments 1-9 further including:    adding a fourth plurality of emulsifying agents to the fifth mixture    before mixing the fifth mixture with the sixth mixture, wherein: the    second plurality of emulsifying agents has a second    hydrophilic-lipophilic balance value; the fourth plurality of    emulsifying agents has a third hydrophilic-lipophilic balance value;    and the third hydrophilic-lipophilic balance value is higher than    the second hydrophilic-lipophilic balance value.-   11. The method of any one of embodiments 1-10, wherein: the first    plurality of active ingredients includes a source of cannabinoids,    wherein the source of cannabinoids is selected from the group    consisting of cannabigerol, cannabigerolic acid, cannabigerolic acid    monomethylether, cannabigerol monomethyl ether, cannabichromene,    cannabichromanon, cannabichromenic acid, cannabichromevarin,    cannabichromevarinic acid, cannabidiol, tetrahydrocannabinol,    iso-tetrahydrocannabinol-type, cannabinol, cannabinolic acid,    cannabinol methylether, cannabicyclol-type, cannabicyclolic acid,    cannabicyclovarin, cannabicitran, cannabitriol, cannabitriolvarin,    cannabivarin, cannabifuran, and cannabiripsol.-   12. The method of any one of embodiments 1-11, wherein: the first    plurality of lipophilic carriers is selected from the group    consisting of short-chain triglycerides, medium-chain triglycerides,    long-chain triglycerides, medium-chain partial glycerides,    polyoxyethylated fatty alcohols, polyethylene glycol, and vegetable    oil.-   13. The method of any one of embodiments 1-12, wherein: mixing the    first mixture with the second mixture is done at a first shear rate;    mixing the third mixture with the fourth mixture is done at a second    shear rate; and the first shear rate is higher than the second shear    rate.-   14. The method of any one of embodiments 1-13, wherein: the seventh    mixture includes: a dispersion medium including the sixth mixture;    and a dispersed phase including droplets of the fifth mixture.-   15. The method of any one of embodiments 1-14, wherein: the droplets    of the fifth mixture have a mean diameter of less than 1 micron.-   16. The method of any one of embodiments 1-15 further including:    cooling the seventh mixture to a fifth temperature, wherein: the    first polymer has a first glass transition temperature; the third    polymer has a second glass transition temperature; and the fifth    temperature is less than the first and the second glass transition    temperatures.-   17. The method of any one of embodiments 1-16, wherein: the first    plurality of active ingredients is selected from the group    consisting of hemp, Cannabis, Echinacea purpurea, Echinacea    angustifolia, Echinacea pallida, Acmella oleracea, Helichrysum    umbraculigerum, Radula marginata, kava, black truffle, Syzygium    aromaticum, Rosmarinus oficinalis, basil, oregano, lavender, true    cinnamon, malabathrum, Cananga odorata, Riboflavin, Theanine, Ginkgo    biloba, Bacopa, and Rhodiola Rosea Extract. 18. The method of any    one of embodiments 1-171, wherein: at least 50% by weight of the    first plurality of active ingredients is not released within 30    minutes after consumption of the seventh mixture.-   19. The method of any one of embodiments 1-18, wherein: the weight    ratio of the first mixture to the second mixture is from 1:1.5 to    1:5; the weight ratio of the third mixture to the fourth mixture is    from 1:1.5 to 1:5; and the weight ratio of the fifth mixture to the    sixth mixture is from 1:1.5 to 1:5.-   20. The method of any one of embodiments 1-19, wherein: the fourth    mixture further including: a second plurality of active ingredients,    the second plurality of active ingredients includes: at least one    source of bioavailibity enhancer.

Group B:

-   1. A food and beverage additive having enhanced water solubility,    the additive including: an aqueous solution; a first plurality of    polymers; a first particle including: a first plurality of    lipophilic carriers; a first active ingredient; a first plurality of    emulsifying agents; and a second plurality of polymers; wherein the    first particle exhibits higher hydrophilicity compared to the first    active ingredient; and wherein a plurality of the first particles    are uniformly dispersed in the aqueous solution.-   2. The additive of embodiment 1, wherein: the aqueous solution is at    least 55% by weight of the additive; the first active ingredient is    at least 5% by weight of the additive; the first plurality of    lipophilic carriers is at least 10% by weight of the additive; and    the first active ingredient is less than 50% by weight of the first    plurality of lipophilic carriers.-   3. The additive of any one of embodiments 1-2, the additive further    including: a second plurality of emulsifying agents selected from    the group consisting of an extract of Quillaja, Tween 20, Tween 40,    Tween 45, Tween 60, Tween 65, Tween 80, Tween 81 and Tween 85,    polyglyceryl, gum Acacia, Xanthan gum, sorbitol, mannitol, glycerol,    and sodium alginate.-   4. The additive of any one of embodiments 1-3, wherein: the first    plurality of emulsifying agents has a hydrophilic-lipophilic balance    (HLB) of higher than 8; and the first plurality of emulsifying    agents is more than 25% by weight of the first plurality of    lipophilic carriers.-   5. The additive of any one of embodiments 1-4, the additive further    including: at least one preservative agent selected from the group    consisting of sodium benzoate, sodium metabisulfite, potassium    sorbate, sorbic acid, acetic acid, propionic acid, sulfites,    nitrites, sodium sorbate, calcium sorbate, benzoic acid, and    potassium benzonate.-   6. The additive of any one of embodiments 1-5, the additive further    including: at least one flavoring agent.-   7. The additive of any one of embodiments 1-6, wherein: the first    particle has a Z-average diameter of smaller than 1 micron, when    tested by Dynamic Light Scattering.-   8. The additive of any one of embodiments 1-7, wherein: the first    particle has a Z-average diameter of smaller than 200 nm, when    tested by Dynamic Light Scattering.-   9. The additive of any one of embodiments 1-7, wherein: the first    particle has a Z-average diameter of smaller than 500 nm; and the    additive can be stored at room temperature for at least 12 months,    with less than 20% change in the Z-average diameter of the first    particle.-   10. The additive of any one of embodiments 1-7, wherein: the second    plurality of polymers has a first glass transition temperature,    wherein the first glass transition temperature is higher than 100°    C.; the first particle has a Z-average diameter of smaller than 500    nm; and the additive can be stored at temperatures below 85° C. for    at least 30 minutes, with less than 20% change in the Z-average    diameter of the first particle.-   11. The additive of embodiment any one of embodiments 1-10, wherein:    the plurality of the first particles has a polydispersity of less    than or equal to 0.25.-   12. The additive of embodiment any one of embodiments 1-11, wherein:    the aqueous solution is selected from the group consisting of:    water, saline, propylene glycol, or combinations thereof.-   13. The additive of embodiment any one of embodiments 1-12, wherein:    the first active ingredient has a concentration of at least 40    milligram per milliliter of the additive.-   14. The additive of embodiment any one of embodiments 1-13, wherein:    the first active ingredient includes a source of cannabinoids,    wherein the source of cannabinoids is selected from the group    consisting of cannabigerol, cannabigerolic acid, cannabigerolic acid    monomethylether, cannabigerol monomethyl ether, cannabichromene,    cannabichromanon, cannabichromenic acid, cannabichromevarin,    cannabichromevarinic acid, cannabidiol, tetrahydrocannabinol,    iso-tetrahydrocannabinol-type, cannabinol, cannabinolic acid,    cannabinol methylether, cannabicyclol-type, cannabicyclolic acid,    cannabicyclovarin, cannabicitran, cannabitriol, cannabitriolvarin,    cannabivarin, cannabifuran, and cannabiripsol.-   15. The additive of embodiment any one of embodiments 1-14, wherein:    at least 30% by weight of the first active ingredient is not    released within 60 minutes after consumption.-   16. The additive of embodiment any one of embodiments 1-15, the    first particle further including: at least one source of    bioavailibity enhancer.-   17. The additive of embodiment any one of embodiments 1-16, wherein:    the second plurality of polymers includes ethylcellulose.-   18. The additive of embodiment any one of embodiments 1-17, the    first particle further including: at least one wax having a melting    points exceeding 45° C.-   19. The additive of embodiment any one of embodiments 1-18, the    first particle further including: a second active ingredient,    wherein the second active ingredient is selected from the group    consisting of hemp, Cannabis, Echinacea purpurea, Echinacea    angustifolia, Echinacea pallida, Acmella oleracea, Helichrysum    umbraculigerum, Radula marginata, kava, black truffle, Syzygium    aromaticum, Rosmarinus oficinalis, basil, oregano, lavender, true    cinnamon, malabathrum, Cananga odorata, Riboflavin, Theanine, Ginkgo    biloba, Bacopa, and Rhodiola Rosea Extract.-   20. The additive of embodiment any one of embodiments 1-19, wherein:    the first plurality of lipophilic carriers is selected from the    group consisting of short-chain triglycerides, medium-chain    triglycerides, long-chain triglycerides, medium-chain partial    glycerides, polyoxyethylated fatty alcohols, polyethylene glycol,    and vegetable oil.

Group C:

-   1. A bead for use in beverage and food, the bead including: a core    including: a continuous phase including: a lipophilic carrier; and a    wax; a dispersed phase including: a particle including: a first    active ingredient; and a first polymer; and a first shell    substantially surrounding the core.-   2. The bead of embodiment 1, wherein the continuous phase further    including: a second polymer selected from the group consisting of    shellac, methyl cellulose, hydroxy propyl cellulose,    hydroxypropyl-methyl cellulose, ethyl methyl cellulose, carboxy    methyl cellulose, ethyl cellulose, microcrystalline cellulose,    cellulose, hypro mellose, hydroxyl propyl methyl cellulose, or    combinations thereof-   3. The bead of embodiment 2, wherein the second polymer is dissolved    in the lipophilic carrier.-   4. The bead of embodiment any one of embodiments 1-3, wherein the    continuous phase further including: an emulsifying agent, wherein    the emulsifying agent has a hydrophilic-lipophilic balance less than    5.-   5. The bead of embodiment any one of embodiments 1-4, wherein: the    wax is selected from the group consisting of bees wax, carnauba wax,    rice bran wax, camauba wax, candelilla wax, or combinations thereof.-   6. The bead of embodiment any one of embodiments 1-5, wherein: at    least 20% by weight of the first active ingredient is released    within 60 minutes after consumption; and at least 20% by weight of    the first active ingredient is not released within 4 hours after    consumption.-   7. The bead of embodiment any one of embodiments 1-6, the bead    further including: a second shell substantially surrounding the    core, wherein: the second shell is water insoluble; and the second    shell retards the release of the first active ingredient after    consumption.-   8. The bead of embodiment any one of embodiments 1-7, wherein the    particle further including: an aqueous solution selected from the    group consisting of: water, saline, propylene glycol, or    combinations thereof.-   9. The bead of embodiment any one of embodiments 1-8, wherein: the    particle has a Z-average diameter of smaller than 1 micron, when    tested by Dynamic Light Scattering.-   10. The bead of embodiment any one of embodiments 1-8, wherein: the    bead has a Z-average diameter between 400-800 microns.-   11. The bead of embodiment any one of embodiments 1-10, wherein: a    plurality of the beads is administered in one capsule as a single    dose.-   12. The bead of any one of embodiments 1-10, wherein: a plurality of    the beads is administered in a 1 to 2 ounces shot as a single dose.-   13. The bead of embodiment 1, wherein: the first shell further    including: a second active ingredient, wherein the second active    ingredient is different from the first active ingredient.-   14. The bead of embodiment 14, wherein: the first and the second    ingredients are selected from the group consisting of hemp,    Cannabis, Echinacea purpurea, Echinacea angustifolia, Echinacea    pallida, Acmella oleracea, Helichrysum umbraculigerum, Radula    marginata, kava, black truffle, Syzygium aromaticum, Rosmarinus    oficinalis, basil, oregano, lavender, true cinnamon, malabathrum,    Cananga odorata, Riboflavin, Theanine, Ginkgo biloba, Bacopa, and    Rhodiola Rosea Extract.-   15. The bead of embodiment 14, wherein: the first active ingredient    reduces the effect of the second active ingredient.-   16. The bead of embodiment 1, wherein: the first shell includes a    material or combination of materials that do not break down in an    aqueous solution with a pH above 5.5.-   17. The bead of any one of embodiments 1-16, wherein: the first    shell includes a material or combination of materials that do not    break down in an aqueous solution with a pH in the range of 2.0 to    5.0.-   18. The bead of any one of embodiments 1-17, wherein: the first    active ingredient is caffeine and a single dose to be administered    includes an amount of 100 to 700 mg.-   19. The bead of any one of embodiments 1-18, wherein: the first    polymer is selected from the group consisting of alginic acid,    sodium alginate, potassium alginate, calcium alginate, agar, guar    gum, and xanthan gum.

Group D:

-   1. A method of encapsulation, the method including: providing a    first mixture, the first mixture including: a first carrier; and a    first active ingredient; applying heat to the first mixture until    the first mixture reaches a first temperature; providing a second    mixture, the second mixture including: a second carrier; and a first    emulsifying agent; applying heat to the second mixture until the    second mixture reaches a second temperature; mixing the first    mixture with the second mixture to obtain a third mixture, wherein:    the mixing is performed at a third temperature; and the third    temperature is lower than the first temperature; and cooling the    third mixture until the third mixture reaches a fourth temperature,    wherein: the second carrier is in solid state at the fourth    temperature.-   2. The method of embodiment 1 further including: spray drying the    third mixture to obtain a first plurality of beads, wherein: the    first plurality of beads has a Z-average diameter less than 500    microns; and coating the first plurality of beads with a first    layer, wherein: the first layer is water insoluble; and the first    layer retards the release of the first active ingredient after    consumption.-   3. The method of embodiment 1 further including: grinding the third    mixture to obtain a first plurality of beads, wherein: the first    plurality of beads has a Z-average diameter between 400 to 800    microns; and spherinizing the first plurality of beads.-   4. The method of embodiment 3 further including: coating the first    plurality of beads with a first layer, wherein: the first layer is    water insoluble; and the first layer retards the release of the    first active ingredient after consumption.-   5. The method of embodiment 4, wherein: the first layer is a    cellulose-based material.-   6. The method of embodiment 4, wherein: the first plurality of beads    dispersed in a beverage are stable for at least 6 months.-   7. The method of embodiment 4, wherein: the coating of the first    layer is carried out in a fluidized bed.-   8. The method of embodiment 4 further including: coating the first    plurality of beads with a second layer, wherein: the second layer is    water insoluble; and the second layer includes a material or    combination of materials that do not break down in an aqueous    solution with a pH above 5.5.-   9. The method of embodiment 4, wherein: at least 20% by weight of    the first active ingredient is not released within 2 hours after    consumption.-   10. The method of embodiment 4, wherein: the first layer has a    thickness less than 50 microns.-   11. The method of any one of embodiments 1-10, wherein the first    mixture further including: an aqueous solution selected from the    group consisting of: water, saline, propylene glycol, or    combinations thereof; and a first polymer selected from the group    consisting of alginic acid, sodium alginate, potassium alginate,    calcium alginate, agar, guar gum, and xanthan gum.-   12. The method of any one of embodiments 1-11, wherein the second    carrier includes: a wax is selected from the group consisting of    bees wax, carnauba wax, rice bran wax, camauba wax, candelilla wax,    or combinations thereof-   13. The method of any one of embodiments 1-12, wherein the second    carrier includes: a first lipophilic carrier selected from the group    consisting of short-chain triglycerides, medium-chain triglycerides,    long-chain triglycerides, medium-chain partial glycerides,    polyoxyethylated fatty alcohols, polyethylene glycol, and vegetable    oil; and a second polymer selected from the group consisting of    shellac, methyl cellulose, hydroxy propyl cellulose,    hydroxypropyl-methyl cellulose, ethyl methyl cellulose, carboxy    methyl cellulose, ethyl cellulose, microcrystalline cellulose,    cellulose, hypro mellose, hydroxyl propyl methyl cellulose, or    combinations thereof-   14. The method of any one of embodiments 1-13, wherein: the first    emulsifying agent has a hydrophilic-lipophilic balance less than 5.-   15. The method of any one of embodiments 1-14, wherein: the first    emulsifying agent is selected from the group consisting of an    extract of Quillaja, Tween 20, Tween 40, Tween 45, Tween 60, Tween    65, Tween 80, Tween 81 and Tween 85, polyglyceryl, gum Acacia,    Polyglycerol polyricinoleate, Span 85, Span 65, Span 83, Span 80,    Span 60, Span 40, Xanthan gum, sorbitol, mannitol, glycerol, sodium    alginate, or combinations thereof.-   16. The method of any one of embodiments 1-15, wherein the first    mixture further including: a second emulsifying agent selected from    the group consisting of an extract of Quillaja, Tween 20, Tween 40,    Tween 45, Tween 60, Tween 65, Tween 80, Tween 81 and Tween 85,    polyglyceryl, gum Acacia, Polyglycerol polyricinoleate, Span 85,    Span 65, Span 83, Span 80, Span 60, Span 40, Xanthan gum, sorbitol,    mannitol, glycerol, sodium alginate, or combinations thereof-   17. The method of any one of embodiments 1-16, wherein the second    mixture further includes: a water insoluble material, wherein: the    water insoluble material retards the release of the first active    ingredient after consumption.-   18. The method of any one of embodiments 1-17, wherein the second    mixture further includes: a second active ingredient, wherein: the    second active ingredient is different from the first active    ingredient.-   19. The method of embodiment 18, wherein: the first and the second    ingredients are selected from the group consisting of probiotics,    caffeine, hemp, Cannabis, Echinacea purpurea, Echinacea    angustifolia, Echinacea pallida, Acmella oleracea, Helichrysum    umbraculigerum, Radula marginata, kava, black truffle, Syzygium    aromaticum, Rosmarinus oficinalis, basil, oregano, lavender, true    cinnamon, malabathrum, Cananga odorata, Riboflavin, Theanine, Ginkgo    biloba, Bacopa, and Rhodiola Rosea Extract.-   20. The method of any one of embodiments 1-19, wherein: the weight    ratio of the first mixture to the second mixture is from 1:1.5 to    1:5.

Group E:

-   1. A composition for oral administration, the composition including:    a dispersion medium including: an aqueous solution; and a dispersed    phase including: a population of particles, each particle including:    a core including: a first active ingredient; and an aqueous    solution; a shell, substantially surrounding the core, the shell    including: a lipophilic carrier; and a plurality of emulsifying    agents; wherein the particle retards the release of the first active    ingredient after consumption.-   2. The composition of embodiment 1, wherein: the population of    particles has a Z-average diameter less than 1 micron.-   3. The composition of embodiment 2, wherein: the population of    particles has a polydispersity of less than or equal to 0.25.-   4. The composition of embodiment 3, wherein: the polydispersity of    the population of particles changes by less than or equal to 100%    upon 6 months of storage at 25° C.-   5. The composition of embodiment 4, wherein: the storage is    performed in an environment with 50% relative humidity.-   6. The composition of embodiment 3, wherein: the polydispersity of    the population of particles changes by less than or equal to 100%    upon 30 minutes of storage at 85° C.-   7. The composition of embodiment 3, wherein: the polydispersity of    the population of particles changes by less than or equal to 20%    upon pasteurization of the composition.-   8. The composition of any one of embodiments 1-7 further including:    a food additive polysaccharide; a flavoring agent; and a    preservative agent.-   9. The composition of any one of embodiments 1-8, wherein the core    further includes: a first polymer selected from the group consisting    of alginic acid, sodium alginate, potassium alginate, calcium    alginate, agar, guar gum, and xanthan gum.-   10. The composition of embodiment 9, wherein: the first polymer is a    chelating agent for the first active ingredient.-   11. The composition of any one of embodiments 1-10, wherein the    shell further includes: a second polymer, wherein the second polymer    is water insoluble.-   12. The composition of embodiment 11, wherein: the second polymer    has a glass transition temperature above 120° C.-   13. The composition of any one of embodiments 1-12, wherein the    shell further includes: a second active ingredient, wherein the    second active ingredient is selected from the group consisting of    hemp, Cannabis, Echinacea purpurea, Echinacea angustifolia,    Echinacea pallida, Acmella oleracea, Helichrysum umbraculigerum,    Radula marginata, kava, black truffle, Syzygium aromaticum,    Rosmarinus oficinalis, basil, oregano, lavender, true cinnamon,    malabathrum, Cananga odorata, Riboflavin, Theanine, Ginkgo biloba,    Bacopa, Rhodiola Rosea Extract, or combinations thereof.-   14. The composition of any one of embodiments 1-13, wherein: the    lipophilic carrier is selected from the group consisting of    short-chain triglycerides, medium-chain triglycerides, long-chain    triglycerides, medium-chain partial glycerides, polyoxyethylated    fatty alcohols, polyethylene glycol, lemon oil, orange oil,    peppermint oil, spearmint oil, Ylang Ylang oil, Lemon Grass oil, Tea    Tree oil, Rosemary oil, Australian Sandalwood oil, Grape fruit oil,    frankincense oil, cedarwood oil, patchouli oil, cinnamon bark oil,    bergamot oil, chamomile oil, Lemon Eucalyptus oil, ginger oil, key    lime oil, Vanilla oil, vegetable oil, or combinations thereof.-   15. The composition of any one of embodiments 1-14, wherein: the    plurality of emulsifying agents is selected from the group    consisting of an extract of Quillaja, Tween 20, Tween 40, Tween 45,    Tween 60, Tween 65, Tween 80, Tween 81 and Tween 85, polyglyceryl,    gum Acacia, Polyglycerol polyricinoleate, Span 85, Span 65, Span 83,    Span 80, Span 60, Span 40, Xanthan gum, sorbitol, mannitol,    glycerol, sodium alginate, or combinations thereof.-   16. The composition of any one of embodiments 1-15, wherein: at    least 60% by weight of the first active ingredient is not released    within 30 minutes after consumption; and at least 80% by weight of    the first active ingredient is not released within 2 hours after    consumption.-   17. The composition of embodiment 1, wherein: at least 10% by weight    of the first active ingredient is not released within 6 hours after    consumption.-   18. The composition of any one of embodiments 1-17, wherein: the    shell do not break down in an aqueous solution with a pH above 5.5.-   19. The composition of any one of embodiments 1-18, wherein the    shell further includes: a wax is selected from the group consisting    of bees wax, carnauba wax, rice bran wax, camauba wax, candelilla    wax, or combinations thereof-   20. The composition of any one of embodiments 1-19, wherein the    shell further includes: at least one source of bioavailibity    enhancer.

Group F:

-   1. A multilayer particle, the particle including: a core including:    a first active ingredient; and a first polymer; a first shell,    substantially surrounding the core, the first shell including: a    second polymer; a second shell, substantially surrounding the first    shell, the second shell including: a third polymer; and a plurality    of emulsifying agents.-   2. The particle of embodiment 1, wherein the core further includes:    an ion exchange resin equilibrated with the first active ingredient.-   3. The particle of embodiment 1, wherein: at least two of the first,    the second, and the third polymers are hydrophobic.-   4. The particle of any one of embodiments 1-3, wherein: at least one    of the second and the third polymers retards the release of the    first active ingredient after consumption.-   5. The particle of any one of embodiments 1-4, wherein: the second    shell is sprayed on the first shell with a centrifugal atomizer.-   6. The particle of any one of embodiments 1-4, wherein: the second    shell is coated on the first shell with a fluidized bed.-   7. The particle of any one of embodiments 1-6, wherein: the second    shell is formed using compression coating.-   8. The particle of any one of embodiments 1-7, wherein: the particle    has a Z-average diameter between 400 to 800 microns.-   9. The particle of embodiment 8, wherein: the core has a diameter    between 20% to 80% of the particle's diameter; the first shell has a    diameter between 5% to 20% of the particle's diameter; and the    second shell has a diameter between 5% to 20% of the particle's    diameter.-   10. The particle of any one of embodiments 1-9, wherein: the    particle has a Z-average diameter less than 1 micron.-   11. The particle of any one of embodiments 1-10, wherein: the    plurality of emulsifying agents is selected from the group    consisting of an extract of Quillaja, Tween 20, Tween 40, Tween 45,    Tween 60, Tween 65, Tween 80, Tween 81 and Tween 85, polyglyceryl,    gum Acacia, Polyglycerol polyricinoleate, Span 85, Span 65, Span 83,    Span 80, Span 60, Span 40, Xanthan gum, sorbitol, mannitol,    glycerol, sodium alginate, or combinations thereof.-   12. The particle of any one of embodiments 1-11, wherein: at least a    portion of the plurality of emulsifying agents is in the core; and    at least a portion of the plurality of emulsifying agents is in the    first shell.-   13. The particle of any one of embodiments 1-12, wherein: at least a    portion of the plurality of emulsifying agents is in the core; at    least a portion of the plurality of emulsifying agents is in the    first shell, and at least a portion of the plurality of emulsifying    agents is in the second shell.-   14. The particle of embodiment any one of embodiments 1-13, wherein    the first shell further including: a second active ingredient.-   15. The particle of embodiment 14, wherein: the first and the second    active ingredients are selected from the group consisting of    probiotics, caffeine, hemp, Cannabis, Echinacea purpurea, Echinacea    angustifolia, Echinacea pallida, Acmella oleracea, Helichrysum    umbraculigerum, Radula marginata, kava, black truffle, Syzygium    aromaticum, Rosmarinus oficinalis, basil, oregano, lavender, true    cinnamon, malabathrum, Cananga odorata, Riboflavin, Theanine, Ginkgo    biloba, Bacopa, and Rhodiola Rosea Extract.-   16. The particle of embodiment 14, wherein: at least one of the    first and the second active ingredients includes a source of    cannabinoids, wherein the source of cannabinoids is selected from    the group consisting of cannabigerol, cannabigerolic acid,    cannabigerolic acid monomethylether, cannabigerol monomethyl ether,    cannabichromene, cannabichromanon, cannabichromenic acid,    cannabichromevarin, cannabichromevarinic acid, cannabidiol,    tetrahydrocannabinol, iso-tetrahydrocannabinol-type, cannabinol,    cannabinolic acid, cannabinol methylether, cannabicyclol-type,    cannabicyclolic acid, cannabicyclovarin, cannabicitran,    cannabitriol, cannabitriolvarin, cannabivarin, cannabifuran, and    cannabiripsol.-   17. The particle of embodiment any one of embodiments 1-16, wherein:    at least one of the first, second, and the third polymers has a    glass transition temperature above 120° C.-   18. The particle of embodiment any one of embodiments 1-17, wherein:    the first, second, and the third polymers selected from the group    consisting of alginic acid, sodium alginate, potassium alginate,    calcium alginate, agar, guar gum, xanthan gum; shellac, methyl    cellulose, hydroxy propyl cellulose, hydroxypropyl-methyl cellulose,    ethyl methyl cellulose, carboxy methyl cellulose, ethyl cellulose,    microcrystalline cellulose, cellulose, hypro mellose, hydroxyl    propyl methyl cellulose, or combinations thereof-   19. The particle of any one of embodiments 1-18, wherein: the    particle is shelf stable for at least 12 months at room temperature.-   20. The particle of any one of embodiments 1-19, wherein the first    shell further includes: a wax selected from the group consisting of    bees wax, carnauba wax, rice bran wax, camauba wax, and candelilla    wax.

Group G:

-   1. A food and beverage additive, the additive including: a first    phase including: a first filler; a second phase, the second phase    including: a second filler; and a third phase, the third phase    including: a third filler; and a fourth phase, the fourth phase    including: a fifth filler; and a first active ingredient.-   2. The additive of embodiment 1, wherein the third phase further    includes: the first active ingredient.-   3. The additive of any one of embodiments 1-2 further including: a    plurality of emulsifying agents selected from the group consisting    of an extract of Quillaja, Tween 20, Tween 40, Tween 45, Tween 60,    Tween 65, Tween 80, Tween 81 and Tween 85, polyglyceryl, gum Acacia,    Polyglycerol polyricinoleate, Span 85, Span 65, Span 83, Span 80,    Span 60, Span 40, Xanthan gum, sorbitol, mannitol, glycerol, sodium    alginate, or combinations thereof.-   4. The additive of embodiment 3, wherein: every one of the first,    the second, the third, the fourth, and the fifth phases has at least    a portion of plurality of emulsifying agents.-   5. The additive of any one of embodiments 1-4, wherein: the first    and third phases are water insoluble; and the second and fourth    phases are aqueous phases.-   6. The additive of any one of embodiments 1-5, wherein: the second    and fourth phases are water insoluble; and the first and third    phases are aqueous phases.-   7. The additive of any one of embodiments 1-6, wherein: the second    filler is selected from selected from the group consisting of    short-chain triglycerides, medium-chain triglycerides, long-chain    triglycerides, medium-chain partial glycerides, polyoxyethylated    fatty alcohols, polyethylene glycol, and vegetable oil, shellac,    methyl cellulose, hydroxy propyl cellulose, hydroxypropyl-methyl    cellulose, ethyl methyl cellulose, carboxy methyl cellulose, ethyl    cellulose, microcrystalline cellulose, cellulose, hypro mellose,    hydroxyl propyl methyl cellulose, or combinations thereof-   8. The additive of any one of embodiments 1-7, wherein: the fifth    filler is selected from is selected from the group consisting of    alginic acid, sodium alginate, potassium alginate, calcium alginate,    agar, guar gum, and xanthan gum.-   9. The additive of any one of embodiments 1-81, wherein the fourth    phase further includes: the second active ingredient, wherein: if    the first active ingredient is water soluble, the second active    ingredient is a hydrophobic compound; and if the first active    ingredient is oil soluble, the second active ingredient is a    hydrophilic compound.-   10. The additive of any one of embodiments 1-9, wherein: the weight    ratio of the second phase to the first phase is from 1:1.5 to 1:5;    the weight ratio of the third phase to the second phase is from    1:1.5 to 1:5; the weight ratio of the fourth phase to the third    phase is from 1:1.5 to 1:5; and the weight ratio of the fifth phase    to the fourth phase is from 1:1.5 to 1:5.-   11. The additive of any one of embodiments 1-10, wherein: the first    filler has a melting point; the additive is chilled by contact with    a surface at a temperature less than the melting point of the first    filler to form flakes.-   12. The additive of any one of embodiments 1-11, wherein: at least    three of the first, the second, the third, the fourth, and the fifth    fillers retard the release of the first active ingredient after    consumption.-   13. The additive of any one of embodiments 1-12, wherein: the first    active ingredient is uniformly distributed in the fifth filler.-   14. The additive of any one of embodiments 1-13, wherein: the    additive is spray dried to obtain a population of beads, wherein:    the population of beads has a Z-average diameter less than 500    microns.-   15. The additive of any one of embodiments 1-14, wherein: the    additive has a Z-average diameter of smaller than one micron; and    the additive can be stored at room temperature for at least 12    months, with less than 50% change in the Z-average diameter of the    additive.-   16. The additive of any one of embodiments 1-15, wherein: the    additive has a Z-average diameter of smaller than 500 nm; and the    additive can be stored at temperatures below 85° C. for at least 30    seconds, with less than 20% change in the Z-average diameter of the    additive.-   17. The additive of embodiment 1, wherein: at least 10% by weight of    the first active ingredient is not released within 2 hours after    consumption.-   18. The additive of any one of embodiments 1-17, wherein: the first    filler do not break down in an aqueous solution with a pH above 5.5.-   19. The additive of any one of embodiments 1-18, wherein the first    filler comprises: a wax is selected from the group consisting of    bees wax, carnauba wax, rice bran wax, camauba wax, candelilla wax,    or combinations thereof.-   20. The additive of any one of embodiments 1-19, wherein: the first    active ingredient is selected from the group consisting of    probiotics, caffeine, Dynamine, hemp, Cannabis, Echinacea purpurea,    Echinacea angustifolia, Echinacea pallida, Acmella oleracea,    Helichrysum umbraculigerum, Radula marginata, kava, black truffle,    Syzygium aromaticum, Rosmarinus oficinalis, basil, oregano,    lavender, true cinnamon, malabathrum, Cananga odorata, Riboflavin,    Theanine, Ginkgo biloba, Bacopa, and Rhodiola Rosea Extract.

1-20. (canceled)
 21. A composition, the composition comprising: a firstphase comprising: a first filler, wherein the first filler is selectedfrom the group consisting of shellac, methyl cellulose, hydroxy propylcellulose, hydroxypropyl-methyl cellulose, ethyl methyl cellulose,carboxy methyl cellulose, ethyl cellulose, microcrystalline cellulose,cellulose, hypro mellose, hydroxyl propyl methyl cellulose, bees wax,carnauba wax, rice bran wax, camauba wax, candelilla wax, orcombinations thereof; a second phase, the second phase comprising: asecond filler, wherein the second filler is selected from the groupconsisting of gum arabic, Acacia, starch, alginic acid, galactomannan,sodium alginate, potassium alginate, calcium alginate, agar, guar gum,xanthan gum, or combinations thereof; and a third phase, the third phasecomprising: a third filler, wherein the third filler is selected fromthe group consisting of shellac, methyl cellulose, hydroxy propylcellulose, hydroxypropyl-methyl cellulose, ethyl methyl cellulose,carboxy methyl cellulose, ethyl cellulose, microcrystalline cellulose,cellulose, hypro mellose, hydroxyl propyl methyl cellulose, bees wax,carnauba wax, rice bran wax, camauba wax, candelilla wax, orcombinations thereof; and a fourth phase, the fourth phase comprising: a fourth filler, wherein the fourth filler is selected from the groupconsisting of gum arabic, Acacia, starch, alginic acid, galactomannan,sodium alginate, potassium alginate, calcium alginate, agar, guar gum,xanthan gum, or combinations thereof; and  a first active ingredient,wherein the first active ingredient is selected from the groupconsisting of caffeine, Echinacea purpurea, Echinacea angustifolia,Echinacea pallida, Acmella oleracea, Helichrysum umbraculigerum, Radulamarginata, kava, kanna, black truffle, Syzygium aromaticum, Rosmarinusoficinalis, basil, oregano, lavender, true cinnamon, malabathrum,Cananga odorata, Riboflavin, theanine, Ginkgo biloba, Bacopa, RhodiolaRosea, or combinations thereof.
 22. The composition of claim 21,wherein: the first phase has the second phase as a dispersed phase in aform of droplets; the second phase has the third phase as a dispersedphase in a form of droplets; and the third phase has the fourth phase asa dispersed phase in a form of droplets.
 23. The composition of claim21, wherein: the first phase is an exterior shell encapsulating thesecond phase; the second phase is a middle shell encapsulating the thirdphase; and the third phase is an inner shell encapsulating the fourthphase as a core.
 24. The composition of claim 21, wherein the thirdphase further comprises: a second active ingredient, wherein the secondactive ingredient is selected from the group consisting of cannabigerol,cannabigerolic acid, cannabigerolic acid monomethylether, cannabigerolmonomethyl ether, cannabichromene, cannabichromanon, cannabichromenicacid, cannabichromevarin, cannabichromevarinic acid, cannabidiol,tetrahydrocannabinol, iso-tetrahydrocannabinol, cannabinol, cannabinolicacid, cannabinol methylether, cannabielsoin, cannabicitran,cannabitriol, cannabivarin, cannabifuran, cannabiripsol, delta-9-THC,delta-8-THC, or combinations thereof.
 25. The composition of claim 24,wherein: at least 80% by weight of the first active ingredient is notreleased within 1 hour after consumption; and at least 80% by weight ofthe second active ingredient is not released within 1 hour afterconsumption.
 26. The composition of claim 21 further comprising: aplurality of emulsifying agents selected from the group consisting of anextract of Quillaja, Tween 20, Tween 40, Tween 45, Tween 60, Tween 65,Tween 80, Tween 81 and Tween 85, polyglyceryl, gum Acacia, Polyglycerolpolyricinoleate, Span 85, Span 65, Span 83, Span 80, Span 60, Span 40,Xanthan gum, sorbitol, mannitol, glycerol, sodium alginate, orcombinations thereof.
 27. The composition of claim 26, wherein: everyone of the first, the second, the third, and the fourth phases has atleast a portion of plurality of emulsifying agents.
 28. The compositionof claim 21, wherein: the first and third phases are water insoluble;and the second and fourth phases are aqueous phases.
 29. The compositionof claim 21, wherein the second phase further comprises: a third activeingredient, wherein the third active ingredient is selected from thegroup consisting of caffeine, Echinacea purpurea, Echinaceaangustifolia, Echinacea pallida, Acmella oleracea, Helichrysumumbraculigerum, Radula marginata, kava, kanna, black truffle, Syzygiumaromaticum, Rosmarinus oficinalis, basil, oregano, lavender, truecinnamon, malabathrum, Cananga odorata, Riboflavin, theanine, Ginkgobiloba, Bacopa, Rhodiola Rosea, or combinations thereof.
 30. Thecomposition of claim 29, wherein: at least 80% by weight of the firstactive ingredient is not released within 1 hour after consumption; andat least 20% by weight of the third active ingredient is released within1 hour after consumption.
 31. The composition of claim 21, wherein thefirst phase further comprises: a fourth active ingredient, wherein thefourth active ingredient is selected from the group consisting ofcannabigerol, cannabigerolic acid, cannabigerolic acid monomethylether,cannabigerol monomethyl ether, cannabichromene, cannabichromanon,cannabichromenic acid, cannabichromevarin, cannabichromevarinic acid,cannabidiol, tetrahydrocannabinol, iso-tetrahydrocannabinol, cannabinol,cannabinolic acid, cannabinol methylether, cannabielsoin, cannabicitran,cannabitriol, cannabivarin, cannabifuran, cannabiripsol, delta-9-THC,delta-8-THC, or combinations thereof.
 32. The composition of claim 31,wherein: at least 80% by weight of the first active ingredient is notreleased within 1 hour after consumption; and at least 20% by weight ofthe fourth active ingredient is released within 1 hour afterconsumption.
 33. The composition of claim 21, wherein: the second phaseto the first phase has a weight ratio from 1:1.5 to 1:5; the third phaseto the second phase has a weight ratio from 1:1.5 to 1:5; and the fourthphase to the third phase has a weight ratio from 1:1.5 to 1:5.
 34. Thecomposition of claim 21, wherein: the first filler has a glasstransition temperature; the composition is chilled by contact with asurface at a temperature less than the glass transition temperature ofthe first filler to form flakes of the first phase.
 35. The compositionof claim 21, wherein: the first filler has a melting temperature,wherein the melting temperature is more than 50 degrees of Celsius; thecomposition is kept at a temperature at least 5 degrees of Celsius lessthan the melting temperature of the first filler.
 36. The composition ofclaim 21, wherein: at least two of the first, the second, the third, andthe fourth fillers retard release of the first active ingredient afterconsumption.
 37. The composition of claim 21, wherein: the first activeingredient is uniformly distributed in the fourth filler.
 38. Thecomposition of claim 21, wherein: the composition has a Z-averagediameter of smaller than 500 microns; and the composition has a minimumshelf life of 12 months at room temperature.
 39. The composition ofclaim 21, wherein: at least 10% by weight of the first active ingredientis not released within 2 hours after consumption.
 40. The composition ofclaim 21, wherein: at least 80% by weight of the first active ingredientis not released within 1 hour after consumption.
 41. The composition ofclaim 21, wherein: the composition is configured to not release thefirst active ingredient in an aqueous solution with a pH above 5.5. 42.The composition of claim 21, wherein: the composition is configured tonot release the first active ingredient in an aqueous solution with a pHabove 3.0.
 43. A composition, the composition comprising: a first phasecomprising: a first filler, wherein the first filler is selected fromthe group consisting of shellac, methyl cellulose, ethyl cellulose,cellulose, bees wax, carnauba wax, rice bran wax, camauba wax,candelilla wax; a second phase, the second phase comprising: a secondfiller, wherein the second filler is selected from the group consistingof alginic acid, alginate, agar, guar gum, xanthan gum; and a thirdphase, the third phase comprising: a third filler, wherein the thirdfiller is selected from the group consisting of shellac, methylcellulose, ethyl cellulose, cellulose, bees wax, carnauba wax, rice branwax, camauba wax, candelilla wax; and a fourth phase, the fourth phasecomprising:  a fourth filler, wherein the fourth filler is selected fromthe group consisting of alginic acid, alginate, agar, guar gum, xanthangum; and  a first active ingredient, wherein the first active ingredientis selected from the group consisting of caffeine, Echinacea purpurea,Echinacea angustifolia, Echinacea pallida, Acmella oleracea, Helichrysumumbraculigerum, Radula marginata, kava, kanna, black truffle, Syzygiumaromaticum, Rosmarinus oficinalis, basil, oregano, lavender, truecinnamon, malabathrum, Cananga odorata, Riboflavin, theanine, Ginkgobiloba, Bacopa, Rhodiola Rosea.
 44. A composition, the compositioncomprising: a first phase comprising: a first filler, wherein the firstfiller is selected from the group consisting of shellac, methylcellulose, hydroxy propyl cellulose, hydroxypropyl-methyl cellulose,ethyl methyl cellulose, carboxy methyl cellulose, ethyl cellulose,microcrystalline cellulose, cellulose, hypro mellose, hydroxyl propylmethyl cellulose, bees wax, carnauba wax, rice bran wax, camauba wax,candelilla wax, or combinations thereof; a second phase, the secondphase comprising: a second filler, wherein the second filler is selectedfrom the group consisting of gum arabic, Acacia, starch, alginic acid,galactomannan, sodium alginate, potassium alginate, calcium alginate,agar, guar gum, xanthan gum, or combinations thereof; and a third phase,the third phase comprising: a third filler, wherein the third filler isselected from the group consisting of shellac, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl-methyl cellulose, ethyl methylcellulose, carboxy methyl cellulose, ethyl cellulose, microcrystallinecellulose, cellulose, hypro mellose, hydroxyl propyl methyl cellulose,bees wax, carnauba wax, rice bran wax, camauba wax, candelilla wax, orcombinations thereof; and a first active ingredient, wherein the firstactive ingredient is selected from the group consisting of cannabigerol,cannabigerolic acid, cannabigerolic acid monomethylether, cannabigerolmonomethyl ether, cannabichromene, cannabichromanon, cannabichromenicacid, cannabichromevarin, cannabichromevarinic acid, cannabidiol,tetrahydrocannabinol, iso-tetrahydrocannabinol, cannabinol, cannabinolicacid, cannabinol methylether, cannabielsoin, cannabicitran,cannabitriol, cannabivarin, cannabifuran, cannabiripsol, delta-9-THC,delta-8-THC, or combinations thereof.
 45. The composition of claim 44,wherein the third phase further comprises: a fourth phase, the fourthphase comprising: a fourth filler, wherein the fourth filler is selectedfrom the group consisting of gum arabic, Acacia, starch, alginic acid,galactomannan, sodium alginate, potassium alginate, calcium alginate,agar, guar gum, xanthan gum, or combinations thereof; and a secondactive ingredient, wherein the second active ingredient is selected fromthe group consisting of caffeine, Echinacea purpurea, Echinaceaangustifolia, Echinacea pallida, Acmella oleracea, Helichrysumumbraculigerum, Radula marginata, kava, kanna, black truffle, Syzygiumaromaticum, Rosmarinus oficinalis, basil, oregano, lavender, truecinnamon, malabathrum, Cananga odorata, Riboflavin, theanine, Ginkgobiloba, Bacopa, Rhodiola Rosea, or combinations thereof.